Aad pppp 0p 0@  0`0PP@ `0` OHH $ @dˆHHHH̀̀̀ff@1  d Footnote TableFootnote**.\t.\t/ - :;,.!?09 bF% bTOC Heading 1 Heading 2 Heading 3 Heading 4 Heading 5 LORUnresolved Cross-Refs   Default FontDefault FontDefault FontItalicSymbol[LSLC7aJqOPJwxJJJg  f       J     L9 i: i\ieiniziiiiUWW3WAj@UUWgX@k/mkk k;k<?k>kAkEk UN!O!Q"R"V  V!V4"V@#Vf$##$$GK%%%&&''HJ&HK'(())b(**HL)HM**+++.,/,HN+HT,K-L-HU-g.h.>.//001122H/J0J1J2HO3HP4HQ5L"6 3 3HR7h8%4&4=5?5h9h:h;h<x6y6{7|7i =i>88i!?i*@R A99R,B::R8CRADRJE;;RiFRrGR{HU<V<X=Y=RIRJRKRLRM>>RNRORPRQ?? @ @S RSCSSTG[UBACAL:VL<WL=XL>YBBL?ZL;[L@\LA]LB^Gi_CCDDIM`LOaLPbLQc<E=ELRdLFMFJeWGXGH`fLTgHHHahHbiIjIIHckL lL!mJJL7nKKLHoLLL#pMMH&qNNHdr O O P PHes Q QJt "R #RHfuHvHw XS YSHx eT fT hU iU sV tVIy W WL-zI{I|L5}L1~ X XL2IIG"> gY hY Z ZL4 [ [> \ \ ] ] ^ ^ ;_ <_ G` H` Ta UaJO ib jbccddeeffgghhiijjkkllmmnno oY )Z/Z.Z-Y,Y+YE*PkHkLSkOS 1 2 8 59.!`Jo#&')u + i8, h- / 88"}p~pqq8X948urr<'ssttuuJ^c0vvcc1#wwdJ!xxeXyyzz  {{d||7m7l }}~~e%  96()24,66^9E<=9;>1A>MNPQ1>cdf g ;       :+!;":2#  < $:A%:H&;':O(>%):V*=+:],:d-:k. :/<0:1 "#=#2(),-=>ABD E W3W4K!M!O"P"<5:6X#Y#[$\$^%_%=<7:8f&g&i'j';9::r(s(:;=[<:=~))=m>:?**:@:AWB++WC,,:D--..//00;E:F11; G>H>IVJ>K22;L;#M33;N;,O4455;<P66 7 78899PQ::!;";TTR)<*<,=-=/>0>LSA)AWAV&V'V(E?F?H@I@TTOAPAWUZB[B]C^CMVLNCWNL3XoDpDLWLY{E|EN NZFFGGO0!L6[HHIIOr"LG\JJKKO#L$]LLMMO$L&^NNPP%=_>`>5a>b>ic=-d;pe>f>dg>hViOOUqjUkkUllk jPjPjQjQjRjRkSTkVTkZUk]UkaVkdV 37106: Parameter: -r 27477: Parameter: -p +40687: Table: Table 4: Format of Input File 641860: Table Sub: 5A: General Parameters (Part 1 of 2) !22201: Parameter: flexible_ligand 34562: Parameter: orient_ligand 35823: Parameter: score_ligand !36933: Parameter: minimize_ligand "37217: Parameter: multiple_ligands !35897: Parameter: chemical_screen! 14818: Parameter: parallel_jobs& 10903: Parameter: random_seed' *31142: Table Sub: 3B: Chemical Screening . "39224: Parameter: construct_screen/ 11863: Parameter: screen_ligands0 &37989: Parameter: pharmacophore_screen1 #11516: Parameter: similarity_screen2 '36435: Parameter: dissimilarity_maximum3 12413: Parameter: distance_begin4 29001: Parameter: distance_end5 #27220: Parameter: distance_interval6 633669: Table Sub: 3C: Ligand Flexibility (Part 1 of 3); 28389: Parameter: anchor_search@ "18588: Parameter: multiple_anchorsC 34097: Normal: anchor_sizeF *22766: Parameter: write_partial_structuresI 29408: Normal: torsion_driveL 36936: Parameter: clash_overlapS '16303: Parameter: maximum_conformationsT "12399: Parameter: peripheral_seeds_ "32915: Parameter: torsion_minimized )19627: Parameter: reminimize_layer_numbere !42603: Parameter: minimize_anchorf #29269: Parameter: reminimize_anchorg #40569: Parameter: reminimize_ligandh '19540: Parameter: flexible_bond_maximumm *40650: Table Sub: 3D: Orientation Search t &40677: Parameter: match_receptor_sitesu 27719: Parameter: random_searchz &34261: Parameter: match_ligand_centers} "37805: Parameter: uniform_sampling~ $32044: Parameter: total_orientations $20966: Parameter: write_orientations #23984: Parameter: rank_orientations (18391: Parameter: rank_orientation_total (36924: Table Sub: 5E: Match Parameters  24742: Parameter: nodes_minimum 16594: Parameter: nodes_maximum $31851: Parameter: distance_tolerance "36956: Parameter: distance_minimum "20087: Parameter: check_degeneracy 24734: Parameter: reflect_ligand !15625: Parameter: critical_points !18162: Parameter: multiple_points 29119: Parameter: chemical_match 217976: Table Sub: 5F: Multiple Ligand Parameters # !42533: Parameter: ligands_maximum$ 28212: Parameter: initial_skip% 38043: Parameter: interval_skip& %28348: Parameter: heavy_atoms_minimum+ %28023: Parameter: heavy_atoms_maximum, 25701: Parameter: rank_ligands/ #15262: Parameter: rank_ligand_total0 "23603: Parameter: restart_interval1 626630: Table Sub: 5G: Scoring Parameters (Part 1 of 3)4 #27914: Normal: intramolecular_score7 #34124: Normal: intermolecular_score8 41535: Parameter: gridded_score9 22380: Parameter: grid_version< 42188: Parameter: bump_filter= 26093: Parameter: bump_maximum> 36064: Parameter: contact_scoreC '25056: Parameter: contact_clash_overlapD '36640: Parameter: contact_clash_penaltyE 15150: Parameter: chemical_scoreF 23338: Parameter: energy_scoreG #19907: Parameter: dielectric_factorJ 19771: Parameter: atom_modelK 10779: Parameter: vdw_scaleL %36768: Parameter: electrostatic_scaleM 31159: Parameter: rmsd_scoreR !27692: Parameter: contact_maximumS &56025: Parameter: contact_size_penaltyT 21445: Parameter: rmsd_overrideU 022570: Table Sub: 3H: Minimization (Part 2 of 2)X "39678: Parameter: contact_minimizeY %28703: Parameter: initial_translationZ "21978: Parameter: initial_rotation[ !42531: Parameter: initial_torsion^ $19339: Parameter: maximum_iterations_ %17504: Parameter: contact_convergence` 24031: Parameter: maximum_cyclesa #18440: Parameter: cycle_convergenceb %22058: Parameter: contact_terminationc %23238: Table Sub: 3I: Parallel Jobs h !12899: Parameter: parallel_serveri 34401: Parameter: server_namej 17134: Parameter: client_totalk 16643: Parameter: client_name_1n 28290: Parameter: client_nameq )12854: Table Sub: 3J: Input (Part 1 of 2)t "35951: Parameter: ligand_atom_fileu $36287: Parameter: ligand_center_filex $23281: Parameter: receptor_site_filey #31562: Parameter: score_grid_prefixz $27747: Parameter: receptor_atom_file} %14299: Parameter: vdw_definition_file~ *14001: Parameter: chemical_definition_file %10710: Parameter: chemical_match_file %30595: Parameter: chemical_score_file &41113: Parameter: chemical_screen_file &17403: Parameter: flex_definition_file !20042: Parameter: flex_drive_file 36779: Parameter: quit_file 14391: Parameter: dump_file 22639: Table Sub: 3K: Output  K18001: Parameter: ligand_none_file ligand_contact_file ligand_chemical_file $25428: Parameter: ligand_energy_file 24252: Parameter: info_file 13854: Parameter: restart_file% !29815: Parameter: output_molecule( )19748: Parameter: contact_cutoff_distance) 35044: Parameter: chemical_score* (35944: Parameter: energy_cutoff_distance+ 33172: Parameter: atom_model, %12372: Parameter: attractive_exponent/ $24040: Parameter: repulsive_exponent0 %33818: Parameter: distance_dielectric1 #24740: Parameter: dielectric_factor2 23822: Normal: bump_overlap3 !13109: Table Sub: 7C: File Input8 %22067: Parameter: vdw_definition_file; "38720: Table Sub: 7D: File OutputH Q17886: TableFootnote: a. This field is only read during a chemical screening run.l "16301: Heading 1: Reference ManualZ 18568: Heading 2: DOCKcpdistance_toleranceq nodes_minimumr (20437: Heading 3: Command-line Argumentst *34053: Heading 4: Molecule File Conversion 38444: Heading 4: Performance 37839: Heading 2: grid grid 29459: Equation: Equation 2 16624: Equation: Equation 2" 39683: Equation: Equation 5& F17388: Figure: Figure 1. Distance dependence of Lennard-Jones Function0 17041: Equation: Equation 6 and5 19617: Equation: Equation 57 #23197: Equation: Equation 6 , , andD F41920: Figure: Figure 2. Distance dependence of contact score functionL (42263: Heading 3: Command-line ArgumentsX 17338: Heading 2: sphgenYsphgenZmolecular surface[ms`INSPHeclusterladdprhm 33642: Heading 3: autoMSnautoMSuexclude.pdbzcharge}chemprop 38012: Heading 3: clusterclustersphgencolsph 34566: Heading 3: condensecondense conectconvsybfdat2pdb 12611: Heading 3: get_near_resget_near_reshbdata' 33807: Heading 3: idtosyb(idtosyb- 18604: Heading 3: invertPDB.invertPDB5 10859: Heading 3: mol2sph6mol2sph; 28513: Heading 3: ms2dot<ms2dot?oldscore@ 40648: Heading 3: pdb2msApdb2msD 17898: Heading 3: pdb2sybEpdb2sybHpdbrenumIpdbtosphJ 97443: Heading 3: ptrentryM 75291: Heading 3: ptrfieldPqcpe_msY 22646: Heading 3: reformatmsZreformatms]rmsd^ !32170: Heading 2: sdf2mol2, sybdb_sdf2mol2`sdf2mol2 & sybdbasybdbd 28340: Heading 3: showboxeshowboxh 17130: Heading 3: showsphereishowspherensplitmolw #19711: Heading 3: SYBYL MOL2 format} 65381: Heading 3: PDB format 52195: Heading 3: PTR format 78306: Heading 3: SPH format '43103: Heading 4: Atom definition rules /12342: Table: Table 7. Atom definition elements *22276: Table: Table 8. Example definitions 25447: Heading 3: vdw.defn 97377: Heading 3: chem.defn# 45665: Heading 3: chem_match.tbl) 16204: Heading 3: chem_score.tbl/ !23465: Heading 3: chem_screen.tbl5 26494: Heading 3: flex.defn; 25230: Heading 3: flex_drive.tbl? %38035: Heading 2: Appendix 3: Sources@ /21563: Heading 4: Available Chemicals DirectoryA'Available Chemicals DirectoryB /31685: Heading 4: Cambridge Structural DatabaseC-Cambridge Crystallographic DatabaseD !30334: Heading 4: Goodfords gridEGoodfords GRIDF 18574: Heading 4: isisGisisH 24944: Heading 4: msI msL ;11587: Heading 4: Quantum Chemistry Program Exchange (QCPE)M 17787: Heading 4: sybylNsybylU ,16803: Parameter: conformation_cutoff_factor   % / 4 9 A C G R V W Y ] ^ b defghijklmno95_R38444: Heading 4: Performance5_R633669: Table Sub: 3C: Ligand Flexibility (Part 1 of 3)5_R)*40650: Table Sub: 3D: Orientation Search 5_R#]626630: Table Sub: 5G: Scoring Parameters (Part 1 of 3)5_R(g022570: Table Sub: 3H: Minimization (Part 2 of 2)5_R.R217976: Table Sub: 5F: Multiple Ligand Parameters 5_R2*31142: Table Sub: 3B: Chemical Screening 5_R6 "37217: Parameter: multiple_ligands5_R: 34562: Parameter: orient_ligand5_R>[ 35823: Parameter: score_ligand5_RB %23238: Table Sub: 3I: Parallel Jobs 5_RF "37217: Parameter: multiple_ligands5_RK 633669: Table Sub: 3C: Ligand Flexibility (Part 1 of 3)5_R $40576: Heading 3: Chemical Screening5_R %31662: Heading 3: Conformation Search5_R %37908: Heading 4: Anchor Search5_R L%15938: Heading 4: Simultaneous Search5_ROh34097: Normal: anchor_size5_RS"18588: Parameter: multiple_anchors5_R Ƣ>41750: Table: Table 7. Partial Structure Filename Construction5_RW!20042: Parameter: flex_drive_file5_R[29408: Normal: torsion_drive5_R`23822: Normal: bump_overlap5_Rd37839: Heading 2: grid5_Rh29408: Normal: torsion_drive5_Rm25447: Heading 3: vdw.defn5_Rr97377: Heading 3: chem.defn5_Rx 45665: Heading 3: chem_match.tbl5_R| !20042: Parameter: flex_drive_file5_R!#27914: Normal: intramolecular_score5_R"#34124: Normal: intermolecular_score5_R#"37217: Parameter: multiple_ligands5_R$29408: Normal: torsion_drive5_Rj&(36924: Table Sub: 5E: Match Parameters 5_R n'$30227: Heading 3: Orientation Search5_R(&40677: Parameter: match_receptor_sites5_R ς)36138: Heading 4: Random Search5_R 7*(13898: Heading 3: Macromolecular Docking5_R+"37805: Parameter: uniform_sampling5_R,27719: Parameter: random_search5_RB-!27692: Parameter: contact_maximum5_R`.29408: Normal: torsion_drive5_R0"37805: Parameter: uniform_sampling5_RO1$32044: Parameter: total_orientations5_R 226030: Heading 4: Matching5_R3!15625: Parameter: critical_points5_R 5%38353: Heading 3: Database Processing5_R624742: Parameter: nodes_minimum5_R7*40650: Table Sub: 3D: Orientation Search 5_R8$20966: Parameter: write_orientations5_RƷ:!22201: Parameter: flexible_ligand5_R<;37839: Heading 2: grid5_R<)19748: Parameter: contact_cutoff_distance5_Rӵ=37839: Heading 2: grid5_R|>29459: Equation: Equation 25_R?"35951: Parameter: ligand_atom_file5_R@$27747: Parameter: receptor_atom_file5_RB!22201: Parameter: flexible_ligand5_R D%38353: Heading 3: Database Processing5_R/E!12899: Parameter: parallel_server5_RF!12899: Parameter: parallel_server5_R H(13898: Heading 3: Macromolecular Docking5_RI41535: Parameter: gridded_score5_RJ 29119: Parameter: chemical_match5_R9K 15150: Parameter: chemical_score5_RrL#11516: Parameter: similarity_screen5_R`M!22201: Parameter: flexible_ligand5_RbN29408: Normal: torsion_drive5_R 3O"37217: Parameter: multiple_ligands5_ROP25701: Parameter: rank_ligands5_RBQ25701: Parameter: rank_ligands5_R0S25701: Parameter: rank_ligands5_RT25701: Parameter: rank_ligands5_R"`U(20437: Heading 3: Command-line Arguments5_R&X29459: Equation: Equation 25_R+0Z28340: Heading 3: showbox5_R/[ 35044: Parameter: chemical_score5_R4\!29815: Parameter: output_molecule5_R:_Q17886: TableFootnote: a. This field is only read during a chemical screening run.5_R>`Q17886: TableFootnote: a. This field is only read during a chemical screening run.5_RCSaQ17886: TableFootnote: a. This field is only read during a chemical screening run.5_RGcF17388: Figure: Figure 1. Distance dependence of Lennard-Jones Function5_RM=p*34053: Heading 4: Molecule File Conversion5_RRfq(20437: Heading 3: Command-line Arguments5_RW6r(20437: Heading 3: Command-line Arguments5_R su17773: Reference: 20. Meng, E.C., Shoichet, B.K. and Kuntz, I.D. Automated docking with grid-based energy evaluation.5_R t29403: Heading 2: References5_R $u34965: Heading 1: Users Guide5_R[v16624: Equation: Equation 25_R_w16624: Equation: Equation 25_RdxF17388: Figure: Figure 1. Distance dependence of Lennard-Jones Function5_Riy29459: Equation: Equation 25_Rmz39683: Equation: Equation 55_Rq{17041: Equation: Equation 6 and5_Rum|29459: Equation: Equation 25_Rz*}#23197: Equation: Equation 6 , , and5_R~-~19617: Equation: Equation 55_R 28340: Heading 3: showbox5_RF41920: Figure: Figure 2. Distance dependence of contact score function5_R  18383: Heading 4: Chemical Score5_Ri97377: Heading 3: chem.defn5_R 16204: Heading 3: chem_score.tbl5_RZ+40687: Table: Table 4: Format of Input File5_R8(42263: Heading 3: Command-line Arguments5_R܀24944: Heading 4: ms5_R17130: Heading 3: showsphere5_RF22646: Heading 3: reformatms5_Rv 33642: Heading 3: autoMS5_R 38012: Heading 3: cluster5_R ̀ (13898: Heading 3: Macromolecular Docking5_R 38012: Heading 3: cluster5_R 17338: Heading 2: sphgen5_R–22646: Heading 3: reformatms5_RE28513: Heading 3: ms2dot5_R12611: Heading 3: get_near_res5_Rh18604: Heading 3: invertPDB5_R̀37839: Heading 2: grid5_Rr17338: Heading 2: sphgen5_R%12611: Heading 3: get_near_res5_RD33642: Heading 3: autoMS5_R12611: Heading 3: get_near_res5_R텀#19711: Heading 3: SYBYL MOL2 format5_RB/31685: Heading 4: Cambridge Structural Database5_R34566: Heading 3: condense5_Rz33642: Heading 3: autoMS5_R18604: Heading 3: invertPDB5_RS!30334: Heading 4: Goodfords grid5_R 17338: Heading 2: sphgen5_R10859: Heading 3: mol2sph5_R17130: Heading 3: showsphere5_R^ 10859: Heading 3: mol2sph5_R!#19711: Heading 3: SYBYL MOL2 format5_R"$"17898: Heading 3: pdb2syb5_R&#12611: Heading 3: get_near_res5_R+؀$40648: Heading 3: pdb2ms5_R/܀%33642: Heading 3: autoMS5_R4b&#19711: Heading 3: SYBYL MOL2 format5_R8ր'17338: Heading 2: sphgen5_R=|(17338: Heading 2: sphgen5_RA)33642: Heading 3: autoMS5_RF*33807: Heading 3: idtosyb5_RKO+52195: Heading 3: PTR format5_RRg,52195: Heading 3: PTR format5_RVـ-17338: Heading 2: sphgen5_R[݀.22646: Heading 3: reformatms5_R`À/33642: Heading 3: autoMS5_RfS0%38035: Heading 2: Appendix 3: Sources5_Rj117338: Heading 2: sphgen5_Ro2#19711: Heading 3: SYBYL MOL2 format5_Rtl337839: Heading 2: grid5_Ry422646: Heading 3: reformatms5_R~517338: Heading 2: sphgen5_RҀ6#19711: Heading 3: SYBYL MOL2 format5_Rƀ765381: Heading 3: PDB format5_R852195: Heading 3: PTR format5_R978306: Heading 3: SPH format5_R:633669: Table Sub: 3C: Ligand Flexibility (Part 1 of 3)5_R;633669: Table Sub: 3C: Ligand Flexibility (Part 1 of 3)5_R&<#19711: Heading 3: SYBYL MOL2 format5_R=52195: Heading 3: PTR format5_R@>*34053: Heading 4: Molecule File Conversion5_RҀ?97443: Heading 3: ptrentry5_RL@75291: Heading 3: ptrfield5_RA17338: Heading 2: sphgen5_RB/12342: Table: Table 7. Atom definition elements5_RC*22276: Table: Table 8. Example definitions5_RxD'43103: Heading 4: Atom definition rules5_RրE'43103: Heading 4: Atom definition rules5_R&F97377: Heading 3: chem.defn5_R G'43103: Heading 4: Atom definition rules5_RlH97377: Heading 3: chem.defn5_REI'43103: Heading 4: Atom definition rules5_RޝJ97377: Heading 3: chem.defn5_RvK'43103: Heading 4: Atom definition rules5_RyL 25230: Heading 3: flex_drive.tbl5_RVM'43103: Heading 4: Atom definition rules5_RN29408: Normal: torsion_drive5_R(O;11587: Heading 4: Quantum Chemistry Program Exchange (QCPE)5_R4P28389: Parameter: anchor_search5_R.Q29408: Normal: torsion_drive5_R FR630944: Heading 5: Pruning the conformation search tree5_RS 16204: Heading 3: chem_score.tbl5_RT!23465: Heading 3: chem_screen.tbl5_R U26494: Heading 3: flex.defn5_RV 25230: Heading 3: flex_drive.tbl <$curpagenum>"<$monthnum>/<$daynum>/<$shortyear>H<$dayname>, <$monthname> <$daynum>, <$year>, <$hour>:<$minute00> <$ampm> <$paratext[Heading 1]> <$paratext[Heading 2]> <$marker1> <$marker2> <$filename><$lastpagenum> <$fullfilename> (Continued) )<$tblsheetnum> of <$tblsheetcount>Pagepage <$pagenum>PageNum <$pagenum>Heading & Page%<$paranum> on page <$pagenum>Section & Page%section <$paranum> on page <$pagenum>Heading<$paranum>Heading Text & Page&<$paratext> on page <$pagenum> Heading Text<$paratext>Heading Number<$paranumonly>Footnote<$paranumonly> Text Lower<$paratext> Reference<$paranumonly>Text<$paratext>FigureFigure <$paranumonly>TableTable <$paranumonly>Dock.Manual.3.GuideWW11xxzzA||A  AA##%%''AAATOCEHHeadingsKQHTMLTAe,bKF533F4 Table 1. F5F-F5F,F-F6F,F,F6F,F-F6F,F-F6F,F-F6F,F-F6F,!h5F63!b4 Table 2. !w,!f5E%,!p,E,,E,E4,E9,E,E;,J5E,H3J3L3Kb/3A: J5J5gT-J5gV-gX,J-g`,J-J,J-J6J-J,J-J6J-J,J-J6J-J,g -J6g-g,g-g 6g-g,J-f6J-J,J-J6J-J,iH5J6333i>/3G: iJ5iL5iV.iF5iX.iZ.i_-iN,ia-ic,ih-i]6ij-il,iq-if6is-iu,i}-io6i-i,i-i{6i-i,i-i6i-i,i-i6i-i,i-i6i-i,U5i6333U/3B: U5U5g2,U5g4,g6,W",g;,W$,W&,W6,W 6W-8W18W8,W:,WD,W46W;8W?8WF,WH,j3,WB6j5,j7,U,j16U,U,U,U6U,U,Wj,U6U8U8Wl,66U,Wh6k,,6666`@@6666U,U,V#,U6V%,V',Vu,V!6Vw,Vy,V7,Vs6V9,V;,VC,V56VE,VG,Vi,VA6Vk,Vm,X-Vg6X-X,X ,X6X ,X,D5X6333&/3C: D5D5h.D5h .h".&2-h,&4-&6,&:-&06&<-&>,c-&86&8&8J,c-c,&B-b6&D-&F,&J-&@6&L9&N,&R-&H6&T-&V,&Z-&P6&\-&^,&j-&X6&l-&n,Xb-&h6Xd-Xu,X-X`6X-X,D5X6x3z3|3(/3D: D5D5h:.D5h<.h>.(*-h/,(,-(.,(2-((6(4-(6,(:-(06(<-(>,(B-(86(D-(F,(J-(@6(L-(N,(R-(H6(T-(V,(Z-(P6(\-(^,(j-(X6(l-(n,(b-(h6(d-(f,h5(`63 3"3h/ 3I: h5h5h.h5h.h.h-h,h-h,h-h6h-h,h-h6h-h,h-h6i-i,i -h6i-i,i-i 6i-i,i$-i6i8i8i&-i(,i--i"6i/-i1,R&5i+6333R/3E: R(5R*5he.R$5hg.hi.R/-hc,R1-R3,R;-R-6R=-R?,RD-R96RF-RH,RM-RB6RO-RQ,RX-RK6RZ-R\,Rl-RV6Rn-Rp,Ru-Rj6Rw-Ry,R~-Rs6R-R,R-R|6R-R,R-R6R-R,R-R6R8R8R-R,R-R6R-R,R-R6R-R,R-R6R-R,R-R6R-R,R-R6R-R,R-R6R-R,R-R6R-R,R-R6R-R,R-R6R8R8R-R,R-R6R-R,R-R6S-S,S-R6S-S,S%-S 6S 6S 6S6S'-S),S-S 6S76S86S-S,D5S6;3=3?3+/3F: D5D5hx.D5hz.h|.+-hv,+-+,+-+6r@@6666+-+,+-+6+-+,,-+6,-,,, -,6, -,,,-, 6,-,,,-,666@@66,-,,,-,6,-,!,,%-,6,'-,),D5,#6w@@@@333,/3H: D5D5h.D5h.h.,-h,,-,,,-,6,--,--,6--- ,---6---,---6Hq6Hr6---,/5-6R3T3/*/ 3J: /5h./5h./E-h,h8h8h8h8/G,/K-/C6/M,/Q-/I6/S,/W-/O6/Y,/]-/U6/_,/c-/[6/e,/i-/a6/k,/o-/g6/q,/u-/m6/w,/{-/s6/},/-/y6/,/-/6/,/-/6/,/-/6/,D5/6 3 3// 3K: D5h.D5h./-h,h8h8h8/,/-/6Hg6Hh6Hl6Hi6Hm-Hn-Ho-Hp-/,/-/6I,D5/6 m3 o3 q32/5A: D5D5D-D52-2,D-262-2,D-262-2,D526 3 3 355/5B: D5D55R-D55T-5V,5Z-5P65\-5^,5t-5X65v-5x,5|-5r65~-5,5-5z65-5,5-565-5,5-5658585-5,5-565-5,5-565-5,5-565-5,5-565-5,5-565-5,D5565858 b3 d36 /5C: D56#-D56%,6)-6!66+,6/-6'661,6T-6-66V,D56R6 3 36c/5D: D56z-D56|,6-6x66,I56~6 3 3I4 Table 4. I5I-I5I,I-I6I,I,I6I,I-I6I,I-I6I,A3.I68A-8C-8D-8E-8F-j-8G-8H-8I-8J-8K-8L-8M-8N-8O-8P-8Q-8R-8&-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8-8~-8-8-8-8-8-8-8-8-8-8-8-8n-8-8-8-8-8-8-8-8-8-8-8-8-8-8-W-8-8-8-8y-9}-9~-9-9-9-9-9-9-9-9-9-9-9-9-9-9-9-9-9-9G-9-9-9-9-9-9-9-9-9-9-9-9,T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T-T- D= D=A+/6A: A5.B5A1,B5A9-B5A;,A?-A7-AA,B",A=-B$,E.B - D= D=E/6B: E.E5E,E5E-E5E,E-E-E,E-E-E,E-E-E,E-E-E,E-E-E,E-E,E,F-E,F ,F,F,F,E.F>c. eD= gD=A/6C: E.E{5E,E}5E-Ey5E,A-E-A,A-A-A,A-A-A,A-A-A,A-A-A,BT-A-BV,EW-BR-EY,Ei-EU-Ek,Eo-Eg-Eq,B-Em-B,B-B-B,B<-B-B>,L5B:-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L-L[-L,L5L,L,L,L-L,L-N5L,N,N5N,N-N=,N-Y*@N;-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-N-OS-OT-OU-OV-OW-OX-OY-OZ-O[-O\-O]-O^-OL-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-O-P,P,P,P,P ,P ,P,P,P ,P,P,P,P,P,P,P,P,P,P,P,O,Pk-Pl-Pm-P}-Po-Pp-Pq-P-Ps-Pt-Pu-Pv-Pw-Px-Py-Pf-V,V,V, + +Y"+Y,@Y0AY(@Y2@b)BY.@b+@b#Cb'@b%@bDb!@b@bEb@b@bFb@b@b Ab@b @bAb @b@aGb@b@aFa@a@aAa@a@aHa@a@YO@a@A+C+YG+YQ@YU@YM@YW@Y@YS@Y@Y@Y@Y@Y@Y@Y@Y@Y@Y@Yz@Y~@Y|@Yt@Yx@Yv@Y@Yr@+++Y+Y@Y@Y@Y@Y@Y@Y@Y@++Y+Z@Z@Y@Z@Z*@Z@+++Z +Z,@Z.@Z2@Z(@ Z6@Z@Z0@@@@@@@Z@Z@Z@Z@FZ@Z}@Z@@@@B@@@@Z@Z@Zu@Z{@@@Zy@Zm@Zs@@@@@@@Zo@Zq@Ze@Zk@h@@Zi@Z]@Zc@@@j@@@@Z_@Za@Z@Z[@K+M+Z+Z@Z@Z@Z@aO@Z@aQ@Z@aM@m+o+q+s+Z+Z@[@[@[@Z@[@[ @[ @[@[@[@[@[@>@@[@]@]@]@]w@]@@@]y@]{@]}@]m@]u@]o@]q@]s@]c@]k@]e@]g@]i@b@@]a@][@]]@]_@]O@]W@]Q@]S@]U@]M@]G@]I@]K@];@]C@=]=@]?@]A@]1@]9@]3@]5@]7@]'@]/@])@]+@]-@]@]%@]@]!@]#@]@]@]@]@]@] @]@] @] @]@\@]@]@]@]@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@p,@\@\@\@\@\@\@p.@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@\@p0@\@\@\@\@\@\@p2@ \@\@\@p4@\@\@\@\@\s@\{@p6@3\u@\w@\y@\i@\q@\k@\m@\o@\_@\g@\a@\c@\e@\U@\]@\W@\Y@\[@\K@\S@\M@\O@\Q@\A@\I@\C@\E@\G@\7@\?@\9@\;@\=@\-@\5@\/@\1@\3@\#@\+@\%@\'@\)@\@\!@\@\@\@\@\@\@\@\@\@\ @\@\ @\ @[@\@[@[@\@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[@[y@[@[{@[}@[@[o@[w@[q@[s@[u@[e@[m@[g@[i@[k@[[@[c@[]@[_@[a@[Q@[Y@[S@[U@[W@[G@[O@[I@[K@[M@c,[E@c,cIc,c*Ic^,c,c ,cZ,c",c,,c$,c.Ic,c0,c,c,c,cJb,c,bLbLbLb,bLbMbNbObPbQb,bLbLbLb,MRY0YB0f-,Nf9,f<,j6f:,f;,bLbObOb,MSMTMUMVMWMX?cY %Z /[%\%0 00%\%0,0-0%\%000%\%010%\%00 3Y[ 40 0 ;]+0]80;]@0 ;] 0 ] 0 ]!(09;9]90j[j0j\j0Y!+[;!0!;"0".0Jn0J4 Table 3. !0&w,'y,),"Y0i,"Z0i2,,00.0-Y8[707;808 08;8080808S;909/08T;9008U0V0YJbN,dn,R[dr0fh0d0f;f0f0f0dq;J]0Jb^ Equation 1c 0c \ee0c{^ Equation 2]0c0c^ Equation 3c^ Equation 4c0d^ Equation 5d0ei_ Figure 1. ef\ed0d]^ Equation 6dO02^ Equation 7i0n^ Equation 8p0w^ Equation 9290|^ Equation 102H00d;d0f'_ Figure 2. e0d;d0fU0fA\fC0fB\fM06`60606;6]607]707 ]606;7]7307]70[7_;7`07h;7v024 Table 5. 04(a4)a[&09D;90909;9090 Yb00;0;00000000000000000000;0000 0 0 0 8 8888800LYZUc 0 0 c 0 0 0 0 c 0 0 0 c 0 ; 0 0 #^ Equation 11 %0 )0 -; /0 9c =0 A; C0 E0 I; K0 Od S0 W0 [0 _0 c0 g0 k0 o0 s0 w0 y0 }0 0 0 0 ec>0>0>0>0>01c50;0gck0o0c0>0ih ZT0TgTgTgTg[TL0A;A 0T0TF;TI0A'0T[T01}[A;A 0A0A(4 Table 6. 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T'HLequal[(*f"Helvetica"fV"Regular"V*)indexes[(*f"Helvetica"fV"Regular"V*)0,1,char[(*f"Helvetica"fV"Regular"V*)e],char[(*f"Helvetica"fV"Regular"V*)j]],sum[(*f"Helvetica"fV"Regular"V*)over[(*f"Helvetica"fV"Regular"V*)indexes[(*f"Helvetica"fV"Regular"V*)0,1,char[(*f"Helvetica"fV"Regular"V*)q],char[(*f"Helvetica"fV"Regular"V*)i]],times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)D],indexes[(*f"Helvetica"fV"Regular"V*)0,1,char[(*f"Helvetica"fV"Regular"V*)r],times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)i],char[(*f"Helvetica"fV"Regular"V*)j]]]]],equal[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)i],num[(*f"Helvetica"fV"Regular"V*)1.00000000,"1"]],times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)l],char[(*f"Helvetica"fV"Regular"V*)i],char[(*f"Helvetica"fV"Regular"V*)g]]]]RPHvc9CpcBp9CpOŌ.'gequal[(*f"Helvetica"fV"Regular"V*)indexes[(*f"Helvetica"fV"Regular"V*)0,1,char[(*f"Helvetica"fV"Regular"V*)E],times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)v],char[(*f"Helvetica"fV"Regular"V*)d],char[(*f"Helvetica"fV"Regular"V*)w]]],plus[(*f"Helvetica"fV"Regular"V*)times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)C],char[(*f"Symbol"fV"Regular"V*)e],indexes[(*f"Helvetica"fV"Regular"V*)1,0,id[(*f"Helvetica"fV"Regular"V*)over[(*f"Helvetica"fV"Regular"V*)times[(*f"Helvetica"fV"Regular"V*)num[(*f"Helvetica"fV"Regular"V*)2.00000000,"2"],char[(*f"Helvetica"fV"Regular"V*)R]],char[(*f"Helvetica"fV"Regular"V*)r]]],char[(*f"Helvetica"fV"Regular"V*)a]]],minus[(*f"Helvetica"fV"Regular"V*)times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)D],char[(*f"Symbol"fV"Regular"V*)e],indexes[(*f"Helvetica"fV"Regular"V*)1,0,id[(*f"Helvetica"fV"Regular"V*)over[(*f"Helvetica"fV"Regular"V*)times[(*f"Helvetica"fV"Regular"V*)num[(*f"Helvetica"fV"Regular"V*)2.00000000,"2"],char[(*f"Helvetica"fV"Regular"V*)R]],char[(*f"Helvetica"fV"Regular"V*)r]]],char[(*f"Helvetica"fV"Regular"V*)b]]]]]]ܙ^7?cs7Uec7U7U'Iequal[(*f"Helvetica"fV"Regular"V*)function[optotal[char[r]],indexes[(*f"Helvetica"fV"Regular"V*)0,1,char[(*f"Helvetica"fV"Regular"V*)E],times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)v],char[(*f"Helvetica"fV"Regular"V*)d],char[(*f"Helvetica"fV"Regular"V*)w]]]],num[(*f"Helvetica"fV"Regular"V*)0.00000000,"0"]]7Q`c M c M M 0'=equal[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)r],times[(*f"Helvetica"fV"Regular"V*)num[(*f"Helvetica"fV"Regular"V*)2.00000000,"2"],char[(*f"Helvetica"fV"Regular"V*)R]]]UgDzc#t DqcDqDqr'/equal[(*f"Helvetica"fV"Regular"V*)indexes[(*f"Helvetica"fV"Regular"V*)0,1,char[(*f"Helvetica"fV"Regular"V*)E],times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)v],char[(*f"Helvetica"fV"Regular"V*)d],char[(*f"Helvetica"fV"Regular"V*)w]]],minus[(*f"Helvetica"fV"Regular"V*)char[epsilon]]]GApovd #""#rъpd !p^prъpl87.'equal[(*f"Helvetica"fV"Regular"V*)indexes[(*f"Helvetica"fV"Regular"V*)0,1,char[(*f"Helvetica"fV"Regular"V*)E],times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)v],char[(*f"Helvetica"fV"Regular"V*)d],char[(*f"Helvetica"fV"Regular"V*)w]]],plus[(*f"Helvetica"fV"Regular"V*)times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)epsilon],id[(*f"Helvetica"fV"Regular"V*)over[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)b],plus[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)a],minus[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)b]]]]],indexes[(*f"Helvetica"fV"Regular"V*)1,0,id[(*f"Helvetica"fV"Regular"V*)over[(*f"Helvetica"fV"Regular"V*)times[(*f"Helvetica"fV"Regular"V*)num[(*f"Helvetica"fV"Regular"V*)2.00000000,"2"],char[(*f"Helvetica"fV"Regular"V*)R]],char[(*f"Helvetica"fV"Regular"V*)r]]],char[(*f"Helvetica"fV"Regular"V*)a]]],minus[(*f"Helvetica"fV"Regular"V*)times[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)epsilon],id[(*f"Helvetica"fV"Regular"V*)over[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)a],plus[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)a],minus[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)b]]]]],indexes[(*f"Helvetica"fV"Regular"V*)1,0,id[(*f"Helvetica"fV"Regular"V*)over[(*f"Helvetica"fV"Regular"V*)times[(*f"Helvetica"fV"Regular"V*)num[(*f"Helvetica"fV"Regular"V*)2.00000000,"2"],char[(*f"Helvetica"fV"Regular"V*)R]],char[(*f"Helvetica"fV"Regular"V*)r]]],char[(*f"Helvetica"fV"Regular"V*)b]]]]]]6Mg`c!$$ M c# M M 0'=equal[(*f"Helvetica"fV"Regular"V*)char[(*f"Helvetica"fV"Regular"V*)r],times[(*f"Helvetica"fV"Regular"V*)num[(*f"Helvetica"fV"Regular"V*)2.00000000,"2"],char[(*f"Helvetica"fV"Regular"V*)R]]]_!ee$&W%E33e%'33$3#$3#2vU33e%&(2vU332vU2vU$eӉvU$evU2vU2r<e%')2r<2vU2r<F4r<e%(*F4r<F4vUF4r<k6r<e%)+k6r<k6vUk6r<8r<e%*,8r<8vU8r<M@r<e%+-M@r<M@vUM@r<OLr<e%,.OLr<OLvUOLr<QXr<e%-/QXr<QXvUQXr<2Õ Hf%.02Õ H2vU2Õ k6Õ Hf%/1k6Õ Hk6vUk6Õ M@Õ Hf%02M@Õ HM@vUM@Õ 3$S2f%133$S22ЩiЩi!2 h53$S2f%24h53$S2k6Щih5Щi!3 ̽3$S2f%35̽3$S2M@Щi̽Щi!4 3$S2f%463$S2QXЩiЩi!5 wՙVS2f%57wՙVS29w!Interatom Distance, AQXÕ Hf%68QXÕ HQXvUQXÕ 2vUf %792vU2vU6vU2vUf %8:2vU2vU6vU2vUf %9;2vU2vU6vU2uÂf %:<2uÂ2uã6u2ZÂf %;=2ZÂ2Zã6Z2vUf%<>2vU2vU6vU2vUf%=?2vU2vU6vU2vUf%>@2vU2vU6vU2vUHf%?A2vUH2vUvU2vUHf%@B2vUH2vUvU2uÂHf%AC2uÂH2uäu2ZÂHf%BD2ZÂH2ZäZ2vUHf%CE2vUH2vUvU2vUHf%DF2vUH2vUvU VS2f%EGVS2\v5Vv5!0 P S2f%FHP S2\v5Pv5!10 Pr_ S2f%GIPr_ S2\xPx!20 PW_ S2f%HJPW_ S2\]P]!30 P S2f%IKP S2\Bv5PBv5!40 P S2f%JLP S2\v5Pv5!50 P S2f%KMP S2\v5Pv5!60 O|S2f%LNEaGS2v5gEg! Score Value2vUHf%MO2vUH2vUvU-vU\)f %NP-vU\)B-vU_g%-Xr? c82? c82vU28<Da~ ~9~xB~$J~~~M@~H~~c~FzN8֣DOLTe$JR:PQX222 zN2&V2^22<2T2 \2$e2 HI,U{וeXHI,U{וHI,@HI,U{U{@HI,U{וeXHI,U{וHI,@HI,U{U{@HI,@Meذ9Xe XMeذ9XMeذW0 \ܭERS2e X \ܭERS2\ܳ\ܳ!6-12 vdwMeػ9XeX Meػ9XMeػW0 \ܸyRS2e X \ܸyRS2\ܾ\ܾ! 6-9 vdwUvs33SeX Uvs33SkkUvIUvIkkkkji eX ji kkjiji eX ji kkjiȀji eX Ȁji ȀkkȀjiji eXji kkjigji eXgji gkkgjinji eXnji nkknji O\ji eX O\ji  O\kk O\jiIji eXIji IkkIjii^eXi^kkiȀi^eXȀi^ȀkkȀigi^eXgi^gkkgi o(S2eXo(S2u@u@!2 o(S2eXo(S2Ȁu@u@!3 lo(S2eXlo(S2gu@lu@!4 o(S2eXo(S2 O\u@u@!5 O\i^eX O\i^ O\kk O\ikk eXkk kk"kkZ2 eXZ2 Z2"Z2J(h eXJ(h J(h"J(h eX  "ҁ eX!ҁ "Uv eX "Uv Uv"Uvkk^eX!#kk^kkStkkZ2^eX"$Z2^Z2StZ2J(h^eX#%J(h^J(hStJ(h^eX$&^Stҁ^eX%'ҁ^St gȏʈS2eX&(gȏʈS2 nl nl !-0.2 WSʈS2eX')WSʈS2 ]B]B!-0.1 F2S2eX(* F2S2 M(w M(w!0 ChS2eX)+ChS2 ҼC!0.1 CnS2eX*,CnS2 ҫC!0.2 CAS2eX+-CAS2 қUCU!0.3Uv^eX,.Uv^UvStUvߘUvJjE e X-/ߘUvJjE /ߘUvе ](0խE0CLdRK9ڒVSj:Y4[K9ߊ\2] 1^p ^,^]g]OQ\K\(hMO[?Zܡ/Z$OEY~lXX ;]s !ROUTPUT FILE Results are written to %output_file, or %dock.out p]if not specified. If a %-o flag is present then &dock runs in batch mode, A-otherwise it runs interactively (see below). }Q$\=?Q$]sW%e-s }uc\>@uc]sWa };\?A;]s!>STANDARD INPUT Parameters are entered interactively without pAthe construction of an input file. This option is generally not A recommended. }Q-$\@BQ-$]sW%mp-r }u-c\ACu-c]sWa }-;\BD-;]s!DRESTART Run is initialized with information from a restart file. pMThis option is used to restart a %rank_ligands docking run that was Aterminated prematurely. }QW$\CEQW$]sW%mp-p }uWc\DFuWc]sWa }W;\EGW;]s!BPROFILE Time spent in docking routines and minimizer statistics pJare profiled. This option helps the user to identify the bottleneck of a Dparticular calculation and to choose optimal minimizer parameters. M5See p'Performance' on page 73p. }Q$ \FHQ$]sW%e-t }uc \GIuc]sWa }; \HJ;]s!DTERSE Reduced output level. This option helps reduce the size of PA:the output file when docking a large number of molecules. }Q$\IKQ$]s W%e-v }uc\JLuc]s Wa };\K;]s !BVERBOSE Increased output level. This option allows additional pDdata to be included in the output. Recommended for single molecule Aruns. }HbOHcu W UTUTipFormat of Input File })b) cu We }Q!bMPQcu W"(aRule }2#bOQ2cu W(a Consequence }Q'bPRQcu $!1Parameter names must be the first word on a line PAto be recognized. }2)bQS2cu !!,Any character or word preceding a parameter PAeffectively comments it out. }Q-bRTQcu &!*The word following a recognized parameter PA,name is interpreted as the parameter value. }2/bSU2cu #!.Comments can appear on the same line, after a PAparameter and value. }Q3bTVQcuW(aBlank lines are allowed. }25bUW2cuW%a'Comments can appear on separate lines. }Q/9bVXQ/cuW*aEmpty files are allowed. }2/;bWY2/cu'!0Missing parameters will be flagged (batch mode) PA!or requested (interactive mode). }QN?bXZQNcuW,a'The order of parameters is irrelevant. }2NAbY[2NcuW)a }H> EbZ_H> cvW0lpGeneralpp }> Gb> cvW-e }> Ib> cvW.e }M> KbM> cvW/e }UPRb[`UPcvW4(` Parameter }P6Tb_aP6cvW+(`Type }$P6Vb`b$P6cvW1(`Default }ZPXbacZPcvW2(` Description }Ud^bbgUdcv8!`Parameters in this category determine the general behavior of the dock run. Each option can be pmused in isolation and many in combination to allow &dock to perform a diverse repertoire of tasks. nIf none of these flags are selected, then &dock simply reads in a single molecule and writes it out, A,which is useful for file format conversion. }d6`bd6cvW3e }$d6bb$d6cvW5e }ZddbZdcvW6e }U™jbchU™cvW<%mp flexible_ligand }™6lbgi™6cvW7%aboolean }$™6nbhj$™6cvW9%ano }Z™pbikZ™cvW:m6Flag to allow p )Ligand Flexibilityp . }U­zbjlU­cvW@%mp orient_ligand }­6|bkm­6cvW;%aboolean }$­6~bln$­6cvW=%ano }Z­bmZ­cvW>m;Flag to perform an p )Orientation Searchp. }UmepUmfvWD%mpscore_ligand }m6eoqm6fvW?%aboolean }$m6epr$m6fvWA%ano }ZmeqsZmfvB,Z |!n Flag to screen based on whether pmolecule keys include @pharmacophore pattern. }U6E U6|"Wt%hp1similarity_screen }66G!66|"Wo%`boolean }$66I "$66|"Wq%`no }Z6K!#Z6|"r &Flag to screen based on similarity of P@molecule keys to target keys. }UUR"$UU|#Wx%hp2dissimilarity_maximum }U6T#%U6|#Ws%`float }$U6V$&$U6|#Wu%`0.25 }ZUX%'ZU|#v %Maximum dissimilarity with target to P@write out molecule. }Ut_&(Ut|$W|%hp3distance_begin }t6a')t6|$Ww%`float }$t6c(*$t6|$Wy%`2 }Zte)+Zt|$z !Smallest distance of interest in P@ fingerprint. }Ul*,U|%W%hp4distance_end }6n+-6|%W{%`float }$6p,.$6|%W}%`17 }Zr-/Z|%~ Largest distance of interest in P@ fingerprint. }UJy.0UJ|&W%hp5distance_interval }6J{/16J|&W%`float }$6J}02$6J|&W%`0.5 }ZJ1ZJJ|& )Distance resolution of fingerprint. The p%total number of distance keys cannot !exceed 30, since a 32-bit key is ¤tly used with the terminal bits !being reserved for out-of-range @values. }H} e7H} fw'Wl(p6Ligand Flexibilityp7p8 }} e} fw'We }} e} fw'We }M} eM} fw'We }Ue38Ufw(W (` Parameter }6e796fw(W(`Type }$6e8:$6fw(W (`Default }Ze9;Zfw(W (` Description }Ue:?Ufw) bLigand flexibility parameters can be used in various combinations to relax an input conformation, pcto perform a conformational search of a molecule, or to perform a completely flexible docking of a L\molecule. See p9'Conformation Search' on page 32p: for more discussion. }6e6fw)W e }$6e$6fw)W e }ZeZfw)We }Ue;@Ufw*W%lp;anchor_search }6e?A6fw*W%`boolean }$6e@B$6fw*W%`no }ZeACZfw* %Flag to organize rigid segments into 0%concentric layers around an anchor. 'Only the anchor is included in initial 'scoring/orienting. The outer segments are reattached in a subsequent @conformation search. %R,6yes = p<'Anchor-First Searchp= is ]D performed. %l,9no = p>'Simultaneous Searchp? of all rw%torsions is performed prior to other @ processing. }UWReBDUWRfw+W%lp@multiple_anchors }W6ReCEW6Rfw+W%`boolean }$W6ReDF$W6Rfw+W%`no }ZWReEZWRRfw+ %Flag to select several anchors for a D molecule. %$&yes = All rigid segments meeting 2 7pA*anchor_sizepB criteria will be tried Dindependently as anchors. S%K`'no = The largest segment is used. }UmhHUmiw,W %hpCanchor_size }m6hGIm6iw,W%`integer }$m6hHJ$m6iw,W%`10 }ZmhIKZmiw, "Minimum number of heavy atoms for p 2an anchor if pD*multiple_anchorspE )requested. If no segment satisfies this #value, then the largest segment is @used. }UkhJLUkiw-$%(pFwrite_partial_structureP@s }6khKM6kiw-W%`boolean }$6khLN$6kiw-W!%`no }ZkhMOZkkiw-" &Flag to write out all partially-built p#structures during the anchor-first "search. This option is useful to %monitor the intermediate stages of a flexible ligand dock run. The %structures from each cycle of growth *are written to a separate file, with each "file name constructed as shown in L)pG'Table 6. on page 34pH. }UhNPUiw.W(%hpItorsion_drive }6hOQ6iw.W#%`boolean }$6hPR$6iw.W%%`no }ZhQSZiw.& !Flag to perform a conformational p'search by driving each torsion through $a set of low-energy dihedral values L3read from the pJ*flex_drive_filepK. }UNhhRTUNhiw/W,%hpLclash_overlap }N6hhSUN6hiw/W'%`real }$N6h hTV$N6hiw/W)%`0.5 }ZNh hUWZNhhiw/* #Amount of atom VDW overlap allowed 0 4during a pM*torsion_drivepN. If two 'ligand atoms approach closer than this &fraction of the sum of the VDW radii, %then the conformation is discarded. LISimilar to pO*bump_overlappP in pQ'gridpR. -%R`#0 = Complete overlap allowed. A.`1 = No overlap allowed. }U`hVXU`iw02%(!pSpTconfigurations_per_cyclP@e }6`hWY6`iw0W+%`integer }$6`!hXZ$6`iw0W/%`25 }Z`#hYZ``iw0!$&Sets the amount of sampling during an 0 )r*anchor_searchr with a 8r*torsion_driver. This value sets the %approximate number of configurations "retained during each cycle of the 0search. See r'Pruning the conformation ' 1search tree' on page 36r for a full BD description. }U9@k\U9lw1W<%hp_torsion_minimize }96Bk[]96lw1W1%`boolean }$96Dk\^$96lw1W9%`no }Z9Fk]_Z9lw1: #Flag to perform torsion relaxation p 2based on p`*intramolecular_scorepa L1and/or pb*intermolecular_scorepc. }UcUSk^`UcUlw2W@%hpdreminimize_layer_number }c6UUk_ac6Ulw2W;%`integer }$c6UWk`b$c6Ulw2W=%`2 }ZcUYkacZcUUlw2> &Number of previous layers to minimize p'while minimizing the current segment. #Only neighboring segments in inner %layers (and their neighbors in outer %layers) are minimized. This feature %helps rescue conformations from dead @ends during the search. }U`kbdUlw3WD%hpeminimize_anchor }6bkce6lw3W?%`boolean }$6dkdf$6lw3WA%`yes }ZfkegZlw3B 'This flag specifies whether the anchor p'is minimized during the initial anchor )docking. In general this flag should be @ turned on. }UkmkfhUklw4WH%hpfreminimize_anchor }6kokgi6klw4WC%`boolean }$6kqkhj$6klw4WE%`yes }ZkskikZkklw4F !If a partially-built molecule is pminimized during conformation %search, but no minimizable bonds are 'active, then a rigid-body minimization )is performed. This flag will force such 'a rigid-body reminimization throughout #the search. This method is a more !expensive (but effective) way to @rescue conformations. }UZJzkjlUZJlw5WL%hpgreminimize_ligand }Z6J|kkmZ6Jlw5WG%`boolean }$Z6J~kln$Z6Jlw5WI%`yes }ZZJkmZZJJlw5J &Flag to reminimize the molecule after p%the conformation search, letting all 'torsions and the anchor position relax simultaneously. This process &resolves any accumulated strain built @up during the search. }UmnpUmow6WP%hphflexible_bond_maximum }m6noqm6ow6WK%`integer }$m6npr$m6ow6WM%`10 }ZmnqsZmow6N$The maximum number of flexible p"bonds allowed in a molecule, when L4pi*multiple_ligandspj are processed. }UUnrtUUow7WT%`write_conformations }6Unsu6Uow7WO%`boolean }$6Untv$6Uow7WQ%`no }ZUnuwZUUow7R When a conformation search is p -performed (pk*torsion_drivepl !selected) without an orientation $search, then multiple conformations may be stored with this flag. !Otherwise, only the best scoring @conformation is written. }UnvxUow8X% write_conformation_totaP@l }6nwy6ow8WS%`integer }$6nxz$6ow8WU%`100 }Zny{Zow8V $This parameter specifies the number pof conformations to store per @ molecule. }HA nzHA ox9W\l(pmOrientation Searchpnpo }A nA ox9WYe }A nA ox9WZe }MA nMA ox9W[e }USn{USox:W`(` Parameter }S6nS6ox:WW(`Type }$S6n$S6ox:W](`Default }ZSnZSox:W^(` Description }UgnUgox;d$`Orienting the ligand is fundamental to the docking process. Orienting is traditionally done by p tpp)Matchingpq. Alternative orienting procedures are also available, particularly the random search, awhich can optionally be run without any site points. For typical uses, the traditional matching L{process is still recommended. Please refer to pr'Orientation Search' on page 28ps for more discussion. }g6ng6ox;W_e }$g6n$g6ox;Wae }ZgnZgox;Wbe }UnUox<Wh%hptmatch_receptor_sites }6n 6ox<Wc%`boolean }$6n $6ox<We%`no }Zn Zox<f 'Flag to perform traditional site point-P@directed matching. }Un Uox=Wl%hpurandom_search }6n 6ox=Wg%`boolean }$6n $6ox=Wi%`no }Zn Zox=j Flag to randomly search ligand @orientations. m,/With pv*match_receptor_sitespw, 0all matches are constructed randomly rather than based on @distance comparisons. nV Otherwise, orientations are 0a randomly constructed inside the !smallest rectangular volume that $encloses all points read in as site @points. o,:See px'Random Search' on page 29py for PDmore discussion. }U_nU_ox>Ws%hpzligand_centers }_6n_6ox>Wk%`boolean }$_6n$_6ox>Wp%`no }Z_nZ_ox>q (Flag to use ligand centers read in from p(a separate file for matching instead of %ligand heavy atoms. Please refer to ;p{'Macromolecular Docking' on page 46p| Dfor more discussion. }UmkqUmkrx?Ww%ip}automated_matching }m6kqm6krx?Wr%aboolean }$m6kq$m6kJrx?t%! yes 2(single  ligand), % no- b- (multiple A ligands) }ZmkqZmkkrx?u!#Flag to let matching proceed in an p"automated fashion until a desired !number of orientations have been &formed. It is recommended for single  ligand dock runs. For database searching, manual matching is recommended because dock then "spends more time on ligands which Aare complementary to the site. }UJqUJrx@W{%ip~maximum_orientations }6Jq6Jrx@Wv%ainteger }$6J!q$6JJrx@x%!5000,  (500 if bautomated matchA ing) }ZJ#qZJJrx@y-/With p*automated_matchingp or p 7p.random_searchp, this sets number of "orientations to generate for each (molecule. Otherwise, it sets the upper $limit on the number of orientations Amade by matching. }U$J0qU$JrxAW%hpwrite_orientations }$6J2q$6JrxAWz%`boolean }$$6J4q$$6JrxAW|%`no }Z$J6qZ$JJrxA} When performing an orientation p%search with rigid ligands, this flag #allows multiple orientations to be !saved. Otherwise, only the best-&scoring orientation of each ligand is @saved. }UoJ=q UoJrxBW%hprank_orientations }o6J?q!o6JrxBW~%`boolean }$o6JAq "$o6JrxBW%`no }ZoJCq!#ZoJJrxB )If multiple orientations are saved, then p$this flag causes orientations to be !ranked by score. Otherwise, all %orientations that pass a cutoff (see 6p*contact_maximump, etc) are written D'out in the order they are encountered. }UMq"$UrxCW%hprank_orientation_total }6Oq#%6rxCW%`integer }$6Qq$&$6rxCW%`100 }ZSq%'ZrxC !Number of ranked orientations to P@store. }UkZq&(UkrxDW `write_configurations }6k\q')6krxDW`boolean }$6k^q(*$6krxDW`no }Zk`q)+ZkkrxD  When performing an orientation psearch in combination with a conformation search 8(p*torsion_drivep selected), this flag allows multiple configurations %(conformations + orientations) to be !saved. Otherwise, only the best-(scoring configuration of each ligand is @saved. }UEiq*,UErxE write_configuration_totP@al }E6kq+-E6rxEW `integer }$E6mq,.$E6rxEW `100 }ZEoq-ZErxE  &Number of configurations to store for P@!each molecule (ranked by score). }H] ut3H] uyFWlpMatchingpp }] wt] uyFWe }] yt] uyFWe }M] {tM] uyFWe }Uot/4UouyGW(a Parameter }o6t35o6uyGW(aType }$o6t46$o6uyGW(aDefault }Zot57ZouyGW(a Description }UJt6;UJJuyH%\Matching is the traditional procedure driving the orientation search in &dock. If p ap*automated_matchingp is selected, then the amount of sampling is controlled by pp.maximum_orientationsp only (and no other matching parameters can be set by the user). If it ]is not selected (manual matching), then the amount of sampling is controlled by the node and [distance parameters. Other constraints on manual matching are available based on chemical Mplabeling or critical clusters. See p'Manual Matching' on page 29p for further discussion. }6Jt6JuyHWe }$6Jt$6JuyHWe }ZJtZJuyHWe }Ut7<UuyIW%ipnodes_minimum }6t;=6uyIW%ainteger }$6t<>$6uyIW%a3 }Zt=?ZuyI!#Smallest number of atom-site point p$interactions needed to construct an A orientation. }Ut>@UuyJW#%hpnodes_maximum }6t?A6uyJW%`integer }$6t@B$6uyJW %`10 }ZtACZuyJ! "Largest number of atom-site point p%interactions considered to construct @an orientation }U"tBDU"uyKW'%hpdistance_tolerance }"6tCE"6uyKW"%`real }$"6tDF$"6uyKW$%`0.25 }Z"tEGZ"uyK% %Maximum difference between all intra-p'ligand and intra-receptor distances in %a match. This is the chief sampling @parameter for matching. }UWtFHUWuyLW+%hpdistance_minimum }W6tGIW6uyLW&%`real }$W6tHJ$W6uyLW(%`2.0 }ZWtIKZWuyL) 'Minimum intra-ligand or intra-receptor p#distance allowed in a match. This !parameter biases matching toward #longer distances which convey more @(information about ligand or site shape. }UtJLUuyMW/%hpcheck_degeneracy }6tKM6uyMW*%`boolean }$6tLN$6uyMW,%`no }ZtMOZuyM- !Flag to discard matches that are P@subsets of larger matches. }UUtNPUUuyNW3%hpreflect_ligand }6UtOQ6UuyNW.%`boolean }$6UtPR$6UuyNW0%`no }ZUtQSZUUuyN1 #Flag to dock the mirror image of a p%ligand to rescue an improper match. #Half of all matches with 4 or more $nodes require reflection, otherwise !they are discarded. Use of this parameter is not generally @ recommended. }U JtRTU JuyOW7%hpcritical_points } 6JtSU 6JuyOW2%`boolean }$ 6JtTV$ 6JuyOW4%`no }Z JtUWZ JJuyO5 "Flag to force matching to include p$members from a particular group (or (groups) of site points in every match. "This parameter is useful to focus %docking around a few key residues in @an active site. }UWtVXUWuyPW;%hpmultiple_points }W6tWYW6uyPW6%`boolean }$W6tXZ$W6uyPW8%`no }ZWtY[ZWuyP9$Flag used in combination with p 6p*critical_pointsp to allow multiple )points from the same critical cluster to @appear in a match. }UŒtZ\UŒuyQW?%hpchemical_match }Œ6t[]Œ6uyQW:%`boolean }$Œ6t\^$Œ6uyQW<%`no }ZŒt]ZŒuyQ= !Flag to use chemical labeling to p#identify bad interactions within a %match so that the orientation can be @'discarded before it is even generated. }H JcH ~RWCl&pMultiple Ligandspp }  ~RW@e }  ~RWAe }M !M ~RWBe }U(_dU~SWG(` Parameter }6*ce6~SW>(`Type }$6,df$6~SWD(`Default }Z.egZ~SWE(` Description }U4fkU~TK,iThe parameters in this category control the processing of a database of ligands. See p'Database R'M:Processing' on page 42p for more discussion. }666~TWFe }$68$6~TWHe }Z:Z~TWIe }UCglU~UWO%hpligands_maximum }6Ekm6~UWJ%`integer }$6Gln$6~UWL%`1000 }ZImoZ~UM !The maximum number of ligands to p#read in from the input file. This @INCLUDES skipped ligands. }UEPnpUE~VWS%hpinitial_skip }E6RoqE6~VWN%`integer }$E6Tpr$E6~VWP%`0 }ZEVqsZE~VQ (The initial number of ligands to skip. p'This is useful to position the reading *stream to a particular point in the input @file. }UzJ]rtUzJ~WWW%hpinterval_skip }z6J_suz6J~WWR%`integer }$z6Jatv$z6J~WWT%`0 }ZzJcuZzJJ~WU (The number of ligands to skip for every p%ligand processed. This is useful to &perform a preliminary scan a database &for timing purposes, or to coordinate "the processing of a database over @multiple machines. }Umj xUm ~XW[%hpheavy_atoms_minimum }m6l wym6 ~XWV%`integer }$m6n xz$m6 ~XWX%`0 }Zmp y{Zm ~XY$#Minimum number of heavy atoms. In p(general, set this to at least three (or +p*nodes_minimump) when an M5p)Orientation Searchp is performed. }U} z|U ~YW_%hpheavy_atoms_maximum }6 {}6 ~YWZ%`integer }$6 |~$6 ~YW\%`100 }Z }Z ~YW]`Maximum number of heavy atoms. }UR ~UR ~ZWc%hprank_ligands }6R 6R ~ZW^%`boolean }$6R $6R ~ZW`%`no }ZR ZRR ~Za`Flag to rank best molecules. d%`%yes = Only top scorers written. e %no =For each molecule, the best r$orientation (or set of orientations 0with p*write_orientationsp) is D written. }U  U  ~[Wi%hprank_ligand_total } 6  6 ~[Wb%`integer }$ 6 $ 6 ~[Wf%`100 }Z  Z  ~[Wg`Number of ranked ligands. }U U ~\Wm%hprestart_interval }6  6 ~\Wh%`integer }$6  $6 ~\Wj%`100 }Z KZ ~\k %Number of ligands to process between P@(each time restart information is saved. }H] wH] xz]WqlpScoringpp }] w] xz]Wne }2] w2] xz]Woe }h] wh] xz]Wpe }Uow Uoxz^Wu(` Parameter } o6w o6xz^Wl(`Type }?o6w?o6xz^Wr(`Default }uowuoxz^Ws(` Description }UwUxz_y _Each orientation is scored according to the options selected in this section. Several scoring p`functions exist and are treated independently of each other. To filter molecules based on more bthan one function simultaneously, you will need to rescore in a subsequent step. Most scoring is @[speeded up by precalculating a potential on a 3D grid, but continuum scoring is available. } 6w 6xz_Wte }?6w?6xz_Wve }uwuxz_Wwe }UwUxz`W}%hpintramolecular_score } 6w 6xz`Wx%`boolean }?6w?6xz`Wz%`no }uwuxz`{ Flag to compute score between p!rigid segments. This feature is 1available if p*flexible_ligandp D is selected. }UwUxzaW%hpintermolecular_score } 6w 6xzaW|%`boolean }?6w?6xzaW~%`no }uwuxza Flag to compute score between P@ligand and receptor. }U w U xzbW%hpgridded_score } 6w! 6xzbW%`boolean }? 6w "? 6xzbW%`yes }u w!#u xzb Flag to use precomputed grids p!to evaluate the score, otherwise a continuous evaluation is @made. }UAw"$UAxzcW %mpgrid_version } A6w#% A6xzcW%areal }?A6 w$&?A6xzcW%a4 }uA w%'uAxzc! Option to select grids computed p 6by current version of p'gridp or by E version 3.5 &chemgrid. }Ukw&(UkxzdW %e grid_points } k6w') k6xzdW%ainteger }?k6w(*?k6xzdW %a1000000 }ukw)+ukxzd !If a version preceding 4 is pselected, then this parameter specifies how many grid points Aare contained in the grids. }U!w*,UxzeW%mpbump_filter } 6#w+- 6xzeW %aboolean }?6%w,.?6xzeW%ano }u'w-/uxze! Flag to screen each orientation p#for clashes with receptor prior to Ascoring and minimizing. }U.w.0UxzfW%mpbump_maximum } 60w/1 6xzfW%ainteger }?62w02?6xzfW%a0 }u4w13uxzf!Maximum number of allowed PAbumps. }U;w24UxzgW%mpcontact_score } 6=w35 6xzgW%aboolean }?6?w46?6xzgW%ano }uAw57uxzgWa!Flag to perform contact scoring. }UHw68UxzhW%econtact_cutoff_distance } 6Jw79 6xzhW%areal }?6Lw8:?6xzhW%a4.5 }uNw9;uxzh%!Interaction distance for contact pscoring. Please refer to ,p*contact_cutoff_distancep Min p'gridp. }U2hZw:<U2hxziW!%mpcontact_clash_overlap } 26h\w;= 26hxziW%areal }?26h^w<>?26hxziW%a0.75 }u2h`w=?u2hhxzi!Amount of VDW overlap 0 allowed. If two atoms approach !closer than this fraction of the !sum of their VDW radii, then the Acontact score is penalized. "%G!0 = Complete overlap RA allowed. S#%aa1 = No overlap allowed. }U›iw>@U›xzjW'%mpcontact_clash_penalty } ›6kw?A ›6xzjW %areal }?›6mw@B?›6xzjW$%a50 }u›owAu›xzj%!Amount that contact score is PApenalized for each clash. }UmvzDUm{zkW+%ipchemical_score } m6xzCE m6{zkW&%aboolean }?m6zzDF?m6{zkW(%ano }um|zEGum{zk)!Flag to perform chemical p#scoring. This feature is included !for experimental purposes only.  Parameterization is left to the Auser. Use at your own risk. }UzFHU{zlW/%ipenergy_score } 6zGI 6{zlW*%aboolean }?6zHJ?6{zlW,%ano }uzIKu{zlW-a Flag to perform energy scoring. }UzJLU{zmW3%aenergy_cutoff_distance } 6zKM 6{zmW.%areal }?6zLN?6{zmW0%a10 }uzMOu{zm1!Maximum distance between two p atoms for their contribution to the energy score to be A computed. }UzNPU{znW7%adistance_dielectric } 6zOQ 6{znW2%aboolean }?6zPR?6{znW4%ayes }uzQSu{zn5!Flag to make the dielectric PA!depend linearly on the distance. }UzRTU{zoW;%ipdielectric_factor } 6zSU 6{zoW6%areal }?6zTV?6{zoW8%a4 }uzUWu{zo9%$Coefficient of the dielectric. See p .p'Equation 1 on page 74p for E context. }U?zVXU?{zpW?%aattractive_exponent } ?6zWY ?6{zpW:%ainteger }??6zXZ??6{zpW<%a6 }u?zY[u?{zp=!Exponent of attractive Lennard-PAJones term for VDW potential. }U^zZ\U^{zqWC%arepulsive_exponent } ^6z[] ^6{zqW>%ainteger }?^6z\^?^6{zqW@%a12 }u^z]_u^{zqA!Exponent of repulsive Lennard-PAJones term for VDW potential. }U}z^`U}{zrWG%ipatom_model } }6z_a }6{zrWB%astring }?}6z`b?}6{zrWD%au }u}zacu}{zrE!!Flag for how to model non-polar A hydrogens. H%!u = United atom model. 2Hydrogens attached to carbons are assigned a zero VDW well-depth and the partial charge is Atransferred to the carbon. I%l!a = All atom model. rwHydrogens attached to carbons have regular VDW well-depth and partial Acharge is not modified. }UzbdU{zsWM%ipvdw_scale } 6zce 6{zsWF%areal }?6zdf?6{zsWJ%a1 }uzegu{zsK!Scaling factor of vdw PAcomponent of energy score. }U<zfhU<{ztWQ%ipelectrostatic_scale } <6zgi <6{ztWL%areal }?<6zhj?<6{ztWN%a1 }u<ziku<{ztO! Scaling factor of electrostatic PAcomponent of energy score. }U[`zjlU[`{zuWU%hprmsd_score } [6`zkm [6`{zuWP%`boolean }?[6`zln?[6`{zuWR%`no }u[`zmu[``{zuS Flag to perform rmsd scoring, pwhich is the rmsd of the molecules in the *p*ligand_atom_filep with respect to the molecule in the .p*receptor_atom_filep. Both molecules must have identical @atoms. }Um }pUm~zvY%hpcontact_maximum Z`chemical_maximum [`energy_maximum A\` rmsd_maximum } m6}oq m6~zvWT%`real }?m6}pr?m6~zvWV%`0 }um}qsum~zvW !If orientations or ligands to be pwritten, but not ranked, then !they must pass this score cutoff @to be written to file. }U}rtU~zw`%hpcontact_size_penalty a`chemical_size_penalty Ab`energy_size_penalty } 6}su 6~zwWX%`real }?6 }tv?6~zwW]%`0 }u"}uwu~zw^ #If ligands to be ranked, then they pmay be penalized by this value !for each heavy atom. This helps correct for the uncomplexed @ score and reduce the size bias. }UJ+}vxUJ~zxWf%hprmsd_override } 6J-}wy 6J~zxW_%`real }?6J/}xz?6J~zxWc%`0 }uJ1}y{uJJ~zxd #If orientations to be written, but pnot ranked, then orientations with an RMSD (with respect to !the input orientation) less than this value are written to file @regardless of score. }HW 8}zHW ~{yWjl"pMinimizationpp }W :}W ~{yWge }W <}W ~{yWhe }MW >}MW ~{yWie }UiE}{Ui~{zWn(` Parameter }i6G}i6~{zWe(`Type }$i6I}$i6~{zWk(`Default }ZiK}Zi~{zWl(` Description }U}JQ}U}JJ~{{r ]Minimization allows on-the-fly adjustment of a molecules orientation and/or conformation to p`improve its score. Though this calculation is CPU intensive, it improves the efficiency of the ]orientation or conformation search. The simplex algorithm uses random displacements to seed ^the search. Consequently, minimization results vary depending on the random seed selected by gthe user and the order of input molecules and site points. If high-quality results are required, then @:repeat the run several times with different random seeds. }}6JS}}6J~{{Wme }$}6JU}$}6J~{{Woe }Z}JW}Z}J~{{Wpe }U]}U~{|vhpcontact_minimize 0`chemical_minimize 4`energy_minimize A5`rmsd_minimize }6_} 6~{|Wq%`boolean }$6a} $6~{|Ws%`n }Zc} Z~{|t #Flags to perform minimization with P@"respect to each scoring function. }Um} U~{}W}hpinitial_translation }6o} 6~{}Wu%`real }$6q} $6~{}Wz%`1 }Zs} Z~{}{ "The maximum initial step size (in p"Angstroms) of the simplex in each &cartesian dimension. The actual step $size is a random value between zero @and this value. }U=z}U=~{~Whpinitial_rotation }=6|}=6~{~W|%`real }$=6~}$=6~{~W~%`0.1 }Z=}Z=~{~ The maximum initial step size p+(unitless) for each axis of rotation. The &quaternion representation is used. A "value of one corresponds to a 180 @degree rotation. }UmUUmU{Whpinitial_torsion }m6Um6U{W%`real }$m6U$m6U{W%`10 }ZmUZmUU{$"The maximum initial step size (in pdegrees) for each torsion when /p*flexible_ligandp set. When 'several layers are minimized together, )the outermost layer gets a full step and )the step for each inner layer is divided @by 2, 3, etc. }UU{W hpmaximum_iterations }66{W%`integer }$6$6{W%`100 }ZZ{ Maximum number of simplex piterations for each cycle of @minimization. }UJUJ{ hpcontact_convergence 7`chemical_convergence 8`energy_convergence Ax`rmsd_convergence }6J6J{W%`real }$6J$6J{W %`0.5 }ZJZJJ{  %Convergence criteria with respect to peach scoring function. At any *iteration, if all vertices of the simplex &have a score within this value of the best score, then minimization @ terminates. }U8 U8{Whpmaximum_cycles }86!86{W %`integer }$86 "$86{W%`1 }Z8!#Z8{ Maximum number of minimization p,cycles. After the first cycle, the initial @%step sizes are divided by 2, 3, etc. }UbJ"$UbJ{Whpcycle_convergence }b6J#%b6J{W%`real }$b6J$&$b6J{W%`1 }ZbJ%'ZbJJ{ "The distance a minimization cycle p'must travel to trigger another cycle. !The vector distance of the final #simplex vertices is used, which is 'normalized with respect to the initial @ step size. }UJ&(UJ{hpcontact_termination y`chemical_termination `energy_termination A`rmsd_termination }6J')6J{W%`real }$6J(*$6J{W%`1 }ZJ)ZJJ{ (If the score is greater than this value p'after a cycle of minimization, then no !more cycles are attempted. This 'parameter is useful to avoid prolonged minimization of unrecoverable @orientations or conformations. }H] /H] }W#l#pParallel Jobspp }] ] }W e }] ] }W!e }M] M] }W"e }Uo+0Uo}W'(a Parameter }o6/1o6}W(aType }$o602$o6}W$(aDefault }Zo13Zo}W%(a Description }UU27UUU}+!^The parallel job parameters provide a convenient way to process a large database of molecules p^and distribute the workload over many computers. One dock job must be configured as a server `job. Any number of other jobs running on separate machines are configured as client jobs. The eserver job reads the entire database and parses molecules out to the client jobs for processing. It _is recommended that the server job be executed on the computer which stores the database. The }server job and each client job requires its own input file. See p'Database Processing' on page 42p for Emore discussion. }6U6U}W&e }$6U$6U}W(e }ZUZU}W)e }U38U}W/%ipparallel_server }6796}W*%aboolean }$6 8:$6}W,%ano }Z 9;Z}-!(Flag to identify this job as the server PAjob. }U:<U} W3%hpserver_name }6;=6} W.%`string }$6<>$6} W0%`server }Z=?Z} 1 #The name used by the server job to P@communicate with client jobs. }U >@U} W7%hpclient_total }6"?A6} W2%`integer }$6$@B$6} W4%`5 }Z&ACZ} 5 !The number of client jobs at the P@disposal of this server job. }U6-BDU6} ;%hpclient_name_1 <`client_name_2 A=`client_name_3 ... }66/CE66} W6%`string }$661DF$66} W8%`clientN }Z63EGZ6} 9,6If p*parallel_serverp set, then this p list of names of client jobs is @ requested. }U`J?FHU`J} WA%hpclient_name }`6JAGI`6J} W:%`string }$`6JCHJ$`6J} W>%`client }Z`JEI_Z`JJ} ?,5If p*parallel_serverp not set, then p*the name of this particular client job is $requested. To be recognized by the &server, this name must be included in -the %client_name_N list supplied to @the server job. }Hf O NHf   WDlpInputpp }f Q f   WBe }_f S _f   WCe }ZxZ KOZx WG(` Parameter }xu\ NPxu W@(`Default }qx^ OQqx WE(` Description }ZOc PTZOO J`3The user must supply several kinds of input files. K/`XCoordinateContains molecules/site points (*.mol2, *.pdb, *.xpdb, *.ptr, *.sph). L`RGridContains precalculated score potentials (*.bmp, *.cnt, *.chm, *.nrg). M`TParameterContains VDW, chemical and flexibility parameters (*.defn, *.tbl). AN`MControlEmpty. Used to interact with a running job (*.quit, *.dump). }uOe uO WFe }qOg qO WHe }Zp QUZ WQ%hpligand_atom_file }ur TVu WI%` ligand.mol2 }qt UWq O File containing ligand atom P@ coordinates. }Zz VXZ WT%hpligand_center_file }u| WYu WP%`ligand_center.sph }q~ XZq R #File containing ligand site points  +(see p'Macromolecular Docking' B'Mon page 46p). }Z% Y[Z% WW%hpreceptor_site_file }%u Z\%u WS%`receptor_site.sph }q% []q% U File containing receptor site P@points. }ZD \^ZD WZ%hpscore_grid_prefix }Du ]_Du WV%` score_grid }qD ^`qD X Prefix for files containing P@precalculated score grids. }Zc _aZc W]%hpreceptor_atom_file }cu `bcu WY%`receptor.mol2 }qc acqc [ File containing receptor atom pcoordinates. Used for continuum (no grids) scoring L0when p*gridded_scorep not set. }Z˜ bdZ˜ W`%hpvdw_definition_file }˜u ce˜u W\%`$PATH/vdw.defn }q˜ dq˜ ^ File containing VDW labels and  1parameters. See pY'vdw.defn' on B'Mpage 105pX. }Zm gZm Wc%hpchemical_definition_file }mu fhmu W_%`$PATH/chem.defn }qm giqm a File containing chemical labels  /and definitions. See p['chem.defn' B'Mon page 106p\. }Z hjZ Wf%hpchemical_match_file }u iku b% $PATH/P@chem_match.tbl }q jlq d$File containing chemical p interaction table for use when -q*chemical_matchq set. See M5p]'chem_match.tbl' on page 107qm. }Z kmZ Wi%hqchemical_score_file }u lnu e% $PATH/P@chem_score.tbl }q moq g$File containing chemical pinteraction table for use when -q*chemical_scoreq set. See M5qn'chem_score.tbl' on page 108qo. }Z npZ Wl%hqchemical_screen_file }u oqu h% $PATH/P@chem_screen.tbl }q prq j$File containing chemical 0interaction table for use when ,q*similarity_screenq set. +See r'chem_screen.tbl' on page B'L109r. }ZA qsZA Wo%hqflex_definition_file }Au rtAu Wk%`$PATH/flex.defn }qA suqA m File containing flexible bond plabels and definitions for use /when q *flexible_ligandq  set. M4See r'flex.defn' on page 110r. }Zv tvZv Wr%hq flex_drive_file }vu uwvu n% $PATH/P@flex_drive.tbl }qv vxqv p$File containing torsion pparameters for a /q *torsion_driveq  search. See M5r'flex_drive.tbl' on page 111r. }Z` wyZ` Wu%hqquit_file }u` xzu` Wq%`*.quit }q`  y{q`` s,-When q*multiple_ligandsq is p!set, this file may be created by #the user at any time to signal the "dock job to terminate execution. 0If q*rank_ligandsq is set, the #best molecules are written to file "and an up-to-date restart file is @ generated. }Z  z|Z  Wx%hqdump_file } u  {} u Wt%`*.dump }q  |q  v,6If q*rank_ligandsq is set, this file pmay be created by the user at #any time to signal the dock job to !write the best molecules to file @and resume execution. }H] H] W{lqOutputqq }] ] Wye }_] _] Wze }Zo %~ZoW~(a Parameter }ou 'ouWw(aDefault }qo )qoW|(a Description }Z@ .Z@@ &a4dock writes up to three kinds of output files. /aSCoordinateContains docked molecules (*.mol2, *.pdb, *.xpdb, *.ptr, *.sph). a.InfoContains current ligand rankings. Aa-RestartContains restart information. }u@ 0u@ W}e }q@ 2q@ We }Z :Z!%iqligand_out_file aligand_contact_file  aligand_chemical_file  iqligand_energy_file A aligand_rmsd_file }u < u!%aligand_out.mol2  aligand_cnt.mol2  aligand_chm.mol2 aligand_nrg.mol2 Aaligand_rms.mol2 }q > q!!Files containing docked, pminimized, rescored, or reformatted molecules for each Atype of scoring. }Z M Z"W%iqinfo_file }u O u"W%a*.info }q Q q"%File containing summary pinformation about the current M'q*rank_ligandsq list. }Z.` Z Z.`#W%iqrestart_file }.u` \ .u`#W%a*.rst }q.` ^q.``#%File containing detailed 0information about current /q*rank_ligandsq  list which is !sufficient for restarting if the current job is prematurely (terminated. See q!'Command-line ' (Arguments' on page 53q" for BErestart instructions. }H j-H .P$Wl#General Parametersq#q$ } l- .P$We }2 n-2 .P$We }h p-h .P$We }U& v-U&.P%W(` Parameter } &6 x- &6.P%W(`Type }?&6 z-?&6.P%W(`Default }u& |-u&.P%W(` Description }U: -U:.P&W!%dcompute_grids } :6 - :6.P&W`boolean }?:6 -?:6.P&W%`no }u: -u:.P&W`Flag to compute scoring grids. }UN -UN.P'W%%d grid_spacing } N6 - N6.P'W `real }?N6 -?N6.P'W"%`0.3 }uN - uN.P'# The distance between grid P@points along each axis. }Um -!Um.P(W)%lq%output_molecule } m6 - " m6.P(W$`boolean }?m6 -!#?m6.P(W&%`no }um -"$um.P(' "Flag to write out the coordinates p of the receptor into a new, cleaned-up file. Atoms are "resorted to put all residue atoms $together. Terminal &sybyl capping groups are merged with the terminal residues. This option can be useful to fix ligands also, so that hydrogens *added by &sybyl are put with the @proper residue.& }H -#(H .Q)W-l#Scoring Parametersq&q' } - .Q)W*e }2 -2 .Q)W+e }h -h .Q)W,e }U, -$)U,.Q*W1(` Parameter } ,6 -(* ,6.Q*W((`Type }?,6 -)+?,6.Q*W.(`Default }u, -*,u,.Q*W/(` Description }U@ -+-U@.Q+W5%dcontact_score } @6 -,. @6.Q+W0%`boolean }?@6 --/?@6.Q+W2%`no }u@ -.0u@.Q+W3` Flag to construct contact grid. }UT -/1UT.Q,W9%lq(contact_cutoff_distance } T6 -02 T6.Q,W4%`real }?T6 -13?T6.Q,W6%`4.5 }uT -24uT.Q,7 Maximum distance between p heavy atoms for the interaction @to be counted as a contact. }U~ -35U~.Q-W=%lq)chemical_score } ~6 -46 ~6.Q-W8%`boolean }?~6 -57?~6.Q-W:%`no }u~ -68u~.Q-W;`!Flag to construct chemical grid. }U’ -79U’.Q.WA%d energy_score } ’6 -8: ’6.Q.W<%`boolean }?’6 -9;?’6.Q.W>%`no }u’ -:u’.Q.W?` Flag to perform energy scoring. }Um 0=Um1Q/WE%lq*energy_cutoff_distance } m6 0<> m61Q/W@%`real }?m6 0=??m61Q/WB%`10 }um 0>@um1Q/C Maximum distance between two p atoms for their contribution to the energy score to be @ computed. }U 0?AU1Q0WI%lq+atom_model } 6 0@B 61Q0WD%`string }?6 0AC?61Q0WF%`u }u 0BDu1Q0G Flag for how to model of non-@polar hydrogens. J% u = United atom model. 2Hydrogens attached to carbons are assigned a zero VDW well-depth and the partial charge is @transferred to the carbon. K%l a = All atom model. rwHydrogens attached to carbons have regular VDW well-depth and partial @charge is not modified. }UB 0CEUB1Q1WO%mq,attractive_exponent } B6 0DF B61Q1WH%ainteger }?B6 0EG?B61Q1WL%a6 }uB 0FHuB1Q1M Exponent of attractive Lennard-pJones term for VDW potential. 2See q-'Equation 1 on page 74q. for D context. }Uw 0GIUw1Q2WS%mq/repulsive_exponent } w6 0HJ w61Q2WN%ainteger }?w6 !0IK?w61Q2WP%a12 }uw #0JLuw1Q2Q!Exponent of repulsive Lennard-PAJones term for VDW potential. }U *0KMU1Q3WW%mq0distance_dielectric } 6 ,0LN 61Q3WR%aboolean }?6 .0MO?61Q3WT%ayes }u 00NPu1Q3U!Flag to make the dielectric PA!depend linearly on the distance. }U 70OQU1Q4W[%mq1dielectric_factor } 6 90PR 61Q4WV%areal }?6 ;0QS?61Q4WX%a4 }u =0RTu1Q4WYaCoefficient of the dielectric. }U D0SUU1Q5W_%e bump_filter } 6 F0TV 61Q5WZ%aboolean }?6 H0UW?61Q5W\%ano }u J0VXu1Q5]! Flag to screen each orientation p#for clashes with receptor prior to Ascoring and minimizing. }U~ P0WYU~1Q6Wc%mq2bump_overlap } 6~ R0XZ 6~1Q6W^%areal }?6~ T0Y[?6~1Q6W`%a0.75 }u~ V0Zu~~1Q6a!Amount of VDW overlap 0 allowed. If the probe atom and the receptor heavy atom approach closer than this !fraction of the sum of their VDW $radii, then the position is flagged A as a bump. d%]!0 = Complete overlap hA allowed. Se%wa1 = No overlap allowed. }Ha _3_Ha 4R7Whl q3File Inputq4q5 }a a3a 4R7Wfe }_a c3_a 4R7Wge }Zs j3\`Zs4R8Wk(a Parameter }su l3_asu4R8Wb(aDefault }qs n3`bqs4R8Wi(a Description }Z s3acZ4R9Wn%ereceptor_file }u u3bdu4R9Wj%areceptor.mol2 }q w3ceq4R9l!#Receptor coordinate file. Partial pcharges and atom types need to A be present. }Z |3dfZ4R:Wq%e box_file }u ~3egu4R:Wm%a site_box.pdb }q 3fhq4R:o-3File containing q6'showboxq7 output p file which specifies boundaries A of grid. }Z 3giZ4R;Wt%mq8vdw_definition_file }u 3hju4R;Wp%a$PATH/vdw.defn }q 3ikq4R;WraVDW parameter file. }Z 3jlZ4R<Wwechemical_definition_file }u 3kmu4R<Wsa$PATH/chem.defn }q 3lnq4R<u!#Chemical label definition file for p ,use when q9*chemical_scoreq: Eset. }HH 3mqHH 4S=Wziq;File Output }H 3H 4S=Wxe }_H 3_H 4S=Wye }ZZ 3nrZZ4S>W}(a Parameter }Zu 3qsZu4S>Wv(aDefault }qZ 3rtqZ4S>W{(a Description }Zn 3suZn4S?W%escore_grid_prefix }nu 3tvnu4S?W|%agrid }qn 3uwqn4S?~!Core file name of grids (file pextension will be appended Aautomatically). }Z 3vxZ4S@W%ereceptor_out_file }u 3wyu4S@W%areceptor_out.mol2 }q 3xq4S@!File for cleaned-up receptor PM.when q<*output_moleculeq= set. }Hz *}Hz+MAW"UTUT`(grid command-line argument summary }lz *lz +MAWe }z *z +MAWe }Q$ *z~Q$+MBW $`flag }uc *}uc+MBW$`optional argument }; *~;+MBW$` behavior }Q$ *Q$+MCW %d-i }uc *uc+MCW%` input_file }; *;+MC  FINPUT FILE Input parameters extracted from %input_file, or R%@grid.in if not specified }Q$ *Q$+MDW%d-o }uc *uc+MDW %` output_file }; *;+MD  POUTPUT FILE Output written to %output_file, or %grid.out if P@not specified }Q$ *Q$+MEW%d-s }uc *uc+MEW` }; * ;+MEW`8STANDARD INPUT Input parameters entered interactively }Q$ * Q$+MFW%d-t }uc * uc+MFW` }; * ;+MFW`TERSE Reduced output level }Q$ * Q$+MGW%d-v }uc * uc+MGW` }; * ;+MGW`!VERBOSE Increased output level }`f=@ `f=@H%`3________________General_Parameters________________ `"flexible_ligand no `"orient_ligand no `#multiple_ligands yes `"score_ligand no `"chemical_screen no `"parallel_jobs no  ` !%`3____________Multiple_Ligand_Parameters____________ "`*ligands_maximum #`!initial_skip 0 $`!interval_skip 0 %` &%`3____________________File_Input____________________ '`(ligand_atom_file old.mol2 (` )%`3____________________File_Output___________________ *`'ligand_none_file new.pdb C+` }_ _I,` -%`6 UUUUUUUUU CCCCCCC SSSSSSS FF/ FFF/ .`3 UU/ UU/ CC/ CC/ SS/ SS/ FF/ FFF/ /`0 UU/ UU/ CC/ CC/ SS/ FFFFF/ 0`0 UU/ UU/ CC/ CC/ SS/ FF/ FF\ 1`1 UU/ UU/ CC/ CC/ SS/ SS/ FF/ FF\ 2`2 UUUUUUUUU/ CCCCCCC/ SSSSSSS/ FF/ FF\ 3` 4` 5%`4University of California at San Francisco, DOCK 4.0 6` 7%`3__________________Job_Information_________________ 8`8launch_time Wed Mar 19 12:05:01 1997 9`*host_name mycomputer :`)memory_limit 126062592 ;`0working_directory /usr/people/user <`$user_name user C=` }g *gJ>%`@_________________________Docking_Results_______________________ ?`Name : ligand1 @`Description : **** A`@Orientations tried : 616 B`@Orientations scored : 500 C` D%`@Best energy score : -59.02 E`@ Intramolecular energy score : 12.18 F`@ Intermolecular energy score : -71.20 G`@RMSD of best energy scorer (A) : 2.39 H` I%`@Elapsed cpu time (sec) : 492.87 CJ` }cf 9cf KK%`@______________________Docking_Performance______________________ L` M%`@Procedure timings time (s) percent N`@Read 0.11 0 O`@Screen 0.00 0 P`@Orientation Search 0.48 0 Q`@Orientation Score 49.90 10 R`@Conformation Anchor 0.05 0 S`@Conformation Peripheral 442.38 90 T`@Other 0.02 0 U`@Total 492.94 100 V`@ W`@Minimizer usage minimum average maximum X`@Calls per molecule 4200 4200 4200 Y`@Score improvement per call 0 2.7e+10 8.7e+13 Z`@Vertices per call 1 3 6 [`@Cycles per call 1 2 5 \`@Iterations per cycle 1 15 100 C]` }fV N6fV7TL^%a$Reading in coordinates of receptor. _a1Merging AMN 163 cap residue with THR1 1 residue. `a5Merging CXL 164 cap residue with ALA162 162 residue. aa3CHARGED RESIDUE THR1 : 1.000 ba3CHARGED RESIDUE ARG9 : 1.000 ca3CHARGED RESIDUE LYS51 : 1.000 da3CHARGED RESIDUE ARG52 : 1.000 ea3CHARGED RESIDUE GLU56 : -1.000 fa3CHARGED RESIDUE ARG57 : 1.000 ga3CHARGED RESIDUE HIP77 : 1.000 ha3CHARGED RESIDUE ASP78 : -1.000 ia3CHARGED RESIDUE LYS127 : 1.000 ja3CHARGED RESIDUE ASP146 : -1.000 ka3CHARGED RESIDUE HIP153 : 1.000 la3CHARGED RESIDUE GLU156 : -1.000 ma3CHARGED RESIDUE LYS161 : 1.000 na3CHARGED RESIDUE ALA162 : -1.000 oa p%a3Total charge on UNNAMED : 4.000 Cqa }W0 d6W0 7WMr%a!Reading in grid box information. saEBox center of mass : -1.315 36.145 21.153 taEBox dimensions : 27.525 26.519 26.686 uaENumber of grid points per side [x y z] : 93 90 90 va3Total number of grid points : 753300 wa x%aGenerating scoring grids. ya3Percent of protein atoms processed : 0 za3Percent of protein atoms processed : 10 {a3Percent of protein atoms processed : 20 |a ...etc... C}a }[+@U rf[+@UUg|N~%a@MOLECULE a Histidine a 20 20 1 0 2 aSMALL a GASTEIGER a**** Aa*Histidine with Main Chain as Rigid Anchor }[H@ {i[H@j|O%`@ATOM `O 1 N1 -1.0947 0.5371 1.7186 N.4 1 <1> 0.2252 `O 2 C2 -0.9885 0.9170 0.2765 C.3 1 <1> 0.0213 `O 3 C3 -0.2043 -0.1565 -0.4766 C.3 1 <1> 0.0354  `O 4 C4 -2.3725 1.0376 -0.3154 C.2 1 <1> 0.0897  `O 5 O5 -2.7546 2.1336 -0.8057 O.co2 1 <1> -0.5442  `O 6 C6 1.1797 -0.2771 0.1153 C.2 1 <1> 0.0328  `O 7 N7 2.2791 0.4215 -0.2757 N.pl3 1 <1> -0.3074  `O 8 C8 1.5387 -1.0911 1.1173 C.2 1 <1> 0.0462 `O 9 C9 3.3256 0.0285 0.4990 C.2 1 <1> 0.0853 `O 10 N10 2.9039 -0.8872 1.3511 N.2 1 <1> -0.2465 `O 11 H11 -1.6259 1.2643 2.2287 H 1 <1> 0.2001 `O 12 O12 -3.1452 0.0423 -0.3188 O.co2 1 <1> -0.5442 `O 13 H13 -0.1461 0.4545 2.1242 H 1 <1> 0.2001 `O 14 H14 -0.4726 1.8710 0.1898 H 1 <1> 0.0918 `O 15 H15 -0.7202 -1.1105 -0.3899 H 1 <1> 0.0385 `O 16 H16 -0.1270 0.1200 -1.5261 H 1 <1> 0.0385 `O 17 H17 2.3126 1.1114 -1.0125 H 1 <1> 0.1528 `O 18 H18 0.8943 -1.7774 1.6466 H 1 <1> 0.0845 `O 19 H19 4.3357 0.4040 0.4286 H 1 <1> 0.1000 A`O 20 H20 -1.5855 -0.3703 1.8010 H 1 <1> 0.2001 }[7@ i[7@j|P%`@BOND ` 1 1 2 1 ` 2 2 3 1 ` 3 2 4 1 ` 4 3 6 1 ` 5 4 5 ar  ` 6 6 7 1 !` 7 6 8 2 "` 8 7 9 1 #` 9 8 10 1 $` 10 9 10 2 %` 11 1 11 1 &` 12 4 12 ar '` 13 1 13 1 (` 14 2 14 1 )` 15 3 15 1 *` 16 3 16 1 +` 17 7 17 1 ,` 18 8 18 1 -` 19 9 19 1 A.` 20 1 20 1 }['@ i['@j|Q/%`@SUBSTRUCTURE Q0`? 1 **** 1 TEMP 0 **** **** 0 ROOT }[F@ i[F@j|R1%` @SET 2`BANCHOR STATIC ATOMS **** Anchor Atom Set 3`1 2 4`ARIGID STATIC BONDS **** Rigid Bond Set A5`2 1 3 }H| lH| mSW8lRequired PTR Fieldsq>q? }?| l?| mSW61e }| l| mSW71e }U`? l U`?mTW;a2These fields must be present in every PTR record. }R lRmTWe } `? l `?mTW9e }U`a? l!U`a?mUW>(aField }R l "RmUW:(aType } `? l!# `?mUW<(a Description }U`a? l"$U`a?mVWA%a }R l#%RmVW=%aString } `? l$& `?mVW?a9Directory path and name of file which contains molecule. }U`a? l%'U`a?mWWD%a }R l&(RmWW@%aInteger } `? l') `?mWWBa#Byte position in file of molecule. }U`a? l(*U`a?mXWG%a }R l)+RmXWCa } `? l*, `?mXWEaEnd of record flag. }H! l+/H! mYWJl.Optional PTR Fieldsq@ 1 of 2qA }?! l?! mYWH1e }! l! mYWI1e }U`3? l,2U`3?mZM dIf these fields are present, they will be read and used to update the molecule. The transformation P@Afields will modify the position or conformation of the molecule. }3R l3RmZWFe } `3? l `3?mZWKe }U`Ra? l/3U`Ra?m[WP(`Field }RR l24RRm[WL(`Type } `R? l35 `R?m[WN(` Description }U`fa? l46U`fa?m\WS%a }fR l57fRm\WO%aReal[3] } `f? l68 `f?m\WQa%XYZ translation vector in Angstroms. }U`za? l79U`za?m]WV%a }zR l8:zRm]WR%aReal[3] } `z? l9; `z?m]WTa2Quaternion rotation vector (unitless, range 0-1). }U`Ža? l:<U`Ža?m^WY%a }ŽR l;=ŽRm^WU%aInteger } `Ž? l<> `Ž?m^WWaNumber of rotatable torsions. }U`¢a? "l=?U`¢a?m_W\%a }¢R $l>@¢Rm_WX%aInteger } `¢? &l? `¢?m_WZa9Flag for chiral reflection (%0 or %1). }U`a? +oBU`a?p`W_%a,, ... }R -oACRp`[%! Integer, PAReal } `? /oBD `?p`W]a#Bond identifier and torsion angle. }U`a?떪 4oCEU`a?떪pa_b%ULUUULm qBbcqC }R 6oDFRpaW^%aInteger } `? 8oEG `?paW`aNumber of chemical keys. }U`ªa?떪 @oFHU`ªa?떪pb_e%ULUUULm"qDbcqE }ªR BoGIªRpbWa%aInteger } `ª? DoHJ `ª?pbWcaFlag for folded chemical keys. }U`U=a?롪 LoIKU`U=a?롪pch%% ,, \ULUUUKM...qFbcqG }U=R NoJLU=RpcWd%aInteger } `U=? PoKM `U=?pcWfa,Chemical key label and distance fingerprint }U`? XoLPU`?pdWki>qHThis field is only read during a chemical screening run. }R ZoRpdWge } `? \o `?pdWie }H< boMSH< peWnlComment PTR FieldsqIqJ }?< do?< peWl1e }< fo< peWm1e }U`N? loPVU`N?pfWqaXThese fields are generated for output only. They are completely ignored during input. }NR noNRpfWje } `N? po `N?pfWoe }U`ba? uoSWU`ba?pgWt(aField }bR woVXbRpgWp(aType } `b? yoWY `b?pgWr(a Description }U`va? ~oXZU`va?phWw%a }vR oY[vRphWs%aInteger } `v? oZ\ `v?phWuaLine position in ptr file. }U`a? o[]U`a?piWz%a }R o\^RpiWv%aInteger } `? o]_ `?piWxa!Line position in input ptr file. }U`a? o^`U`a?pjW}%a }R o_aRpjWy%aString } `? o`b `?pjW{aMolecule name. }U`a? oacU`a?pkW%a }R obdRpkW|%aString } `? oce `?pkW~aMolecule description. }U`a? odfU`a?plW%a }R oegRplW%aInteger } `? ofh `?plWaNumber of bumps. }U`a? ogiU`a?pmW%a }R ohjRpmW%aReal } `? oik `?pmWaContact score. }U`a? ojlU`a?pnW %a }R okmRpnW%aReal } `? oln `?pnWaChemical score. }U`a? omoU`a?poW %a }R onpRpoW%aReal } `? ooq `?poW aTotal energy score. }U`a? oprU`a?ppW%a }R oqsRppW %aReal } `? ort `?ppW a#Intramolecular component of score. }U`*a? osuU`*a?pqW%a }*R otv*RpqW%aReal } `*? ouw `*?pqWa#Intermolecular component of score. }U`>a? ovxU`>a?prW%a }>R owy>RprW%aReal } `>? oxz `>?prWaVDW component of score. }U`Ra? oy{U`Ra?psW%a }RR oz|RRpsW%aReal } `R? o{} `R?psWa"Electrostatic component of score. }U`fa? o|~U`fa?ptW%a }fR o}fRptW%aReal } `f? o~ `f?ptWa1RMS deviation of current orientation from input. }1 x11yu%aname Carbon_sp/sp2 aatom_model either aradius 1.850 awell_depth 0.120  aheavy_flag 1 !avalence 4 "a #%adefinition C $a&_____________________________________ %aname Carbon_All_sp3 &aatom_model all 'aradius 1.800 (awell_depth 0.060 )aheavy_flag 1 *avalence 4 +a ,%adefinition C.3 -a&_____________________________________ .a"name Carbon_United_CH3 /aatom_model united 0aradius 2.000 1awell_depth 0.150 2aheavy_flag 1 3avalence 4 4a 5%adefinition C. ( 3 H ) C6a }? u?vvW8(aelement }ʀ uʀvvW(a function }? u?vwW:a atom type }ʀ uʀvw7!4Specifies partial or complete atom type. A partial p;specification is more general (i.e. "C" versus "C.3"). An A&asterisk (*) specifies ANY atom type. }? u?vxW<%a( ) }ʀ uʀvxW9a4Specifies atoms that must be bonded to parent atom. }? "u?vyW>%a[ ] }ʀ $u ʀvyW;a8Specifies atoms that must NOT be bonded to parent atom. }? (u ?vzW@ainteger }ʀ *u ʀvzW=a5Specifies the number of an atom that must be bonded. }V L .u V Lv{WB(aexample }+ L 0u + Lv{W?(a explanation }V ` 4u V `v|WD%aC.2 ( 2 O.co2 ) }+ ` 6u + `v|WAaA carboxylate carbon. }V t :uV tv}WF%a .3 [ 3 H ] }+ t衪 <u+ t衪v}CULUUUL!:Any sp33 hybridized atom that is not attached to TUKAthree hydrogens. }V – @uV –v~WH%a$C. [ O. ] [ N. [ 2 O.2 ] [ 2 C. ] ] }+ – Bu+ –v~E!*Any carbon not attached to an oxygen or a p5nitrogen (unless the nitrogen is a nitro or tertiary A nitrogen). }_1 F{_11|"I%aname hydrophobic Ja K%a:definition C. [ O. ] [ N. [ 2 O.2 ] [ 2 C. ] ] ( * ) Ladefinition N.pl3 ( 3 C. ) Madefinition Cl ( C. ) Nadefinition Br ( C. ) Oadefinition I ( C. ) Padefinition C.3 [ * ] Qa9________________________________________________________ Raname donor Sa T%adefinition N. ( H ) Uadefinition N.4 [ * ] Va9________________________________________________________ Waname acceptor Xa Y%a&definition O. [ H ] [ N. ] ( * ) Za#definition O.3 ( 1 * ) [ N. ] [a(definition O.co2 ( C.2 ( O.co2 ) ) \a5definition N. [ H ] [ N. ] [ O. ] [ 3 . ] ( * ) ]adefinition O.2 [ * ] ^a9________________________________________________________ _aname polar `a a%adefinition O.3 ( H ) badefinition F [ * ] Cca }`@ c~`@(d%a label null ealabel hydrophobic falabel donor galabel acceptor halabel polar ia j%atable ka1 la 1 1 ma1 0 1 na1 0 0 1 oa"1 0 1 1 1 Cpa }`@ r`@.q%a label null ralabel hydrophobic salabel donor talabel acceptor ualabel polar va w%atable xa0 ya 0 1 za0 -1 -1 {a0 -1 1 -1 |a"0 -1 1 1 1 C}a }`@ `@4~%a label null alabel hydrophobic alabel donor alabel acceptor alabel polar a %atable a0 a 0 1 a0 1 1 a0 1 1 1  a"0 1 1 1 1 C a }`@ `@: %`name sp3-sp3  `drive_id 3  `minimize 1 ` %`'definition .3 [ 3 H ] [ 3 O.co2 ] `'definition .3 [ 3 H ] [ 3 O.co2 ] `)________________________________________ `name sp3-sp2 `drive_id 4 `minimize 1 ` %`'definition .3 [ 3 H ] [ 3 O.co2 ] `(definition .2 [ 2 H ] [ 2 O.co2 ] `)________________________________________ `name sp2-sp2 `drive_id 2 `minimize 0 ` %`'definition .2 [ 2 H ] [ 2 O.co2 ] `'definition .2 [ 2 H ] [ 2 O.co2 ] C` }`@  `@ > %adrive_id 2 !apositions 2 "atorsions 0 180 #a*_________________________________________ $adrive_id 3 %apositions 3 &atorsions -60 60 180 'a*_________________________________________ (adrive_id 4 )apositions 4 *atorsions -90 0 90 180 +a*_________________________________________ ,adrive_id 6 -apositions 6 .a'torsions -150 -90 -30 30 90 150 C/a }Y5 rY5s0%!A 10 CAMYLOFIN_C00000105 **** /marco/db/PA,mol2.95.1/cmc/cmc.2.mol2 46204 }Y5 rY5s 1%!A 5 5 DANAZOL_C00002993 **** db/pEdb3.mol2 14144 5.00991 29.9234 16.2096 0.270641 H1.05337 0.0158567 2 1 20 153.624 21 -28.0673 H 0 2 -32.43 -0.48 -31.95 -32.53 A" 0.09 34.95 }Y57 rY57s 2%!B 1 DAZOQUINAST_C00005118 **** /marco/db/pHmol2.95.1/cmc/cmc.1.mol2 9689688 5 1 0 G10 2d7 35 3fff 0 0 20 f65 0 0 1 21 Gfd 0 0 28 ab7e 0 0 2 0 0 0 0 A:0 0 3 6 c1a 0 0 4 0 0 }$ C$ DeW5eHeadings Table } C DeW3e }  C  DeW4e }$Cl C $ClDe W8 eHeading Level }C C!CDe WG eParagraph Format } C C " CDe W6 e Comments }$Sl C!#$SlDe W; e10 }S C"$SDe W74e Equation } S C#% SDe W9 e }$cl C$&$clDe W> e2 }c C%'cDe g:5%HeadinEg 1 } c C&( cDe W< e }$=lN C')$=lNDe WA e3 }=N C(*=NNDe g=6%HeadinEg 2 } =N C)+ =NDe W? e }$l C*,$lDe WD e4 } C+-De W@7e Heading 3 } C,. De WB e }$l C-/$lDeWG e5 } C.0DeWC8 e Heading 4 }  C/1 DeWE e }$l C02$lDeWJ e8 } C13DeWF9 e Heading 5 }  C24 DeWH e }$l C35$lDeWM e9 } C46DeWI4e New Page }  C57 DeWK e }$l C68$lDeWP e9 } C79DeWL4eNew Page Right }  C8: DeWN e }$l C9;$lDeWS e6 } C:<DeWO:UTUTeTable }  C;= DeWQ e }$l# C<>$lDeWV e7 }% C=?DeWR9 e Table Sub } ' C>@ DeWT e }$ l, C?A$ lDeWY e9 } . 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The receptor 0����psite is characterized by centers, which may come from &sphgen or any other source. The molecule being ����fdocked is characterized ligand centers, which may be its non-hydrogen atoms or volume-filling spheres ����lcalculated in &sphgen. The ligand centers and receptor centers are matched based on comparison of ����cligand-center/ligand-center and receptor-center/receptor-center distances. Sets of ligand centers ����Vmatch sets of receptor centers if all the internal distances match, within a value of %���zqpdistance_tolerance<. Ligand-receptor pairs are added to the set until at least %qqnodes_minimum "����hpairs have been found. At least three pairs must be found to uniquely determine a rotation/translation ����omatrix that will orient the ligand in the receptor site. A least-squares fitting procedure is used (Ferro and ����cHermans, 1977). Once an orientation has been found, it is evaluated by any of several scoring func����utions. &dockM may be used to explore the binding modes of an individual molecule, or be used to screen ���@7a database of molecules to identify potential ligands. L1��`Version 2.0 MA���`)Brian Shoichet, Dale Bodian, Irwin Kuntz N&P��� ndockM version 2.0 was written to give the user greater control over the thoroughness of the matching 2[����qprocedure, and thus over the number of orientations found and the Mcpu time required (Shoichet, Bodian, ����gand Kuntz, 1992). In addition, certain algorithmic shortcomings of earlier versions were overcome. Ver����gsions 2.0 and higher are particularly useful for macromolecular docking (Shoichet and Kuntz, 1991) and ����eapplications which demand detailed exploration of ligand binding modes. In these cases, users are en���@[couraged to run &cluster in conjunction with &sphgen and &dock. O��� iTo allow for greater control over searches of orientation space, the ligand and receptor centers are pre0����lorganized according to their internal distances. Starting with any given center, all the other centers are ����ppresorted into bins based on their distance to the first center. All centers are tried in turn as first po����hsitions, and all the points in a bin which has been chosen for matching are tried sequentially. Ligand ����dand receptor bins are chosen for matching when they have the same distance limits from their respec����ktive first points. The number of centers in each bin determines how many sets of points in the receptor ����gand the ligand will ultimately be compared. In general, the wider the bins, the greater the number of ���@Uorientations generated. Thus, the thoroughness of the search is under user control. P��`Version 3.0 Q ���`)Elaine Meng, Brian Shoichet, Irwin Kuntz R��� eVersion 3.0 retained the matching features of version 2.0, and introduced options for scoring (Meng, 0%����cShoichet, and Kuntz, 1992). Besides the simple contact scores mentioned above, one can also obtain ����omolecular mechanics interaction energies using grid files calculated by &chemgrid (which is now super����qseded by &grid in version 4.0). More information about the ligand and receptor molecules is required to ����hperform these higher-level kinds of scoring. Point charges on the receptor and ligand atoms are needed ����jfor electrostatic scoring, and atom-type information is needed for the van der Waals portion of the force ����gfield score. Input formats (some of them new in version 3.5) are discussed in various parts of the doc����fumentation; one example of a complete format (including point charges and atom type information) is N����sybylM NasciiM (Mmol2) format (Tripos Associates, Inc., St. Louis, MO 63117). Parameterization of the reB����yceptor is discussed in the documentation for &chemgrid. In Ndock, ligand parameters are read in along HH��ˆ�����[�V����HH��ˆ��T[WW ���ff�l�����d�������\��������[[�������� HH��ˆ������ Y����HH��ˆ��� ��� ����[����R���fwith the coordinates; input formats are described below. Currently, the options are: contact scoring 0���ronly, contact scoring plus DelphiM electrostatic scoring, and contact scoring plus force field scoring. ���ASAtom-type information and point charges are not required for contact scoring only. S��aVersion 3.5 TD���aFMike Connolly, Daniel Gschwend, Andy Good, Connie Oshiro, Irwin Kuntz US���!cVersion 3.5 added several features: score optimization, degeneracy checking, chemical matching and ^���Acritical clustering. Vv��aVersion 4.0 W���aTodd Ewing, Irwin Kuntz X���!mVersion 4.0 was a major rewrite and update of &dock. A new matching engine was developed which is p���jmore robust, efficient, and easier to use. Orientational sampling can now be controlled directly by spec���cifying the number of desired orientations. Additional features include chemical scoring, chemical ���A#screening, and ligand flexibility. HH��ˆ�����_�Y����HH��ˆ��X^ZZ���ff�l�����d�������`��������^^�������� HH��ˆ������ \����HH��ˆ��������2L^����Y���a Z ���iqrCommand-line Arguments [��@iqs \&���!ldock may be executed in either interactive or batch mode, depending on whether output is written to a 2���ifile. In interactive mode, the user is requested only for parameters relevant to the particular run and ���jdefault values are provided. This mode is recommended for the initial construction of the input file and ���kfor short calculations. In batch mode, input parameters are read in from the input file and all output is ���hwritten to the output file. This mode is recommended for long calculations once an input file has been ���Agenerated interactively. ] ����aInteractive mode ^%���adock -i dock.in _#���!yWhen launched this way, Pdock will extract all relevant parameters from %dock.in (or any file supplied 0.���by the user). If additional parameters are needed (or if the %dock.in file is non-existent or empty), &dock ���dwill request them one at a time from the user. Reasonable default values are presented. Any param���teters supplied by the user will be automatically appended to the %dock.in file. If the user would like to ���Akchange any previously entered values, the user can edit in the %dock.in file using a text editor. `%^���adock -i a&���aXdock will behave as above, but will assume the input file to be %dock.in. Cb%���adock -s HH��ˆ�����c�\����HH��ˆ��[a]] ���ff�l�����d�������d��������aa�������� HH��ˆ������ _����HH��ˆ���#���#����a����c&���!ndock will run interactively, but will not check any input file for parameters and will not append any en���Atered parameters to a file. d ���a Batch mode e%E���adock -i dock.in -o dock.out f&T���!udock will run in batch mode, extracting all relevant parameters from %dock.in (or any file supplied by 2_���uthe user) and will write out all output to %dock.out (or any file supplied by the user). If any parameters ���hare missing or incorrect, then execution will halt and an appropriate error message will be reported in %���Adock.out. g���a dock -i -o h&���andock will behave as above, but will assume the i/o files to be %dock.in and %dock.out. i%���adock j���!If a file called %INDOCK is present in the current working directory, then &dock will use it as an input file. 0���tOutput will be written to a file called %OUTDOCK. This mode is present for reverse compatibility with pre���A"vious versions of &dock. k ���iqtMolecule File Conversion l%���adock -i old.mol2 -o new.pdb m ���!eIf the input and output file have recognized coordinate file extensions (%*.mol2, *.pdb, *.xpdb, %���t*.sph, *.ptr), then &dock will automatically construct its own parameter input file to perform a file ���Aconversion operation. n K���aMolecule File Input/Output o`���!eAlthough molecule files can be input and output at the command line to perform file conversion, they 0k���jare more commonly specified within the input file to specify such things as the ligand input coordinates, ���fthe receptor site point and atom coordinates, and the ligand output coordinates for each scoring func���htion. When each file name is read in from the input file, it is checked to make sure it has one of the ���precognized file extensions (%*.mol2, *.pdb, *.xpdb, *.sph, *.ptr), so that &dock can identify ���Athe proper the file format. p���a(Passing coordinates through a UNIX pipe q&���!eDock can be run as part of a UNIX pipe of commands, in which molecule coordinates are passed berʪ���atween a series of commands. To configure a dock run to operate within a UNIX pipe, dock must be ���ginstructed to read molecule coordinates from the standard input stream and/or write coordinates to the ���istandard output stream. To do this, the streams must not be in use for interactive processing (ie. dock ���output must be directed to an output file with the %-o command line flag). Within the input file, &dock can ���kbe instructed to use the standard streams for coordinates by using %stdin.ext when specifying the ���vinput file name and% stdout.ext for the output file name. The %*.ext file extension must be one of ���Ahthe coordinate file extensions recognized by &dock so that the proper file format can be used. HH��ˆ�����g�_����HH��ˆ��^d``���ff�l�����d�������h��������dd�������� HH��ˆ������ b����HH��ˆ��˜�����Mnd��osw{�r���a s ���aInput Parameters t J���a File Format u^��@ihquInput parameters may be supplied in a text file. There are few simple format rules for this file. v ;���a Parameters w&O���!mdock has a large number of input parameters because of its wide array of functionality. Parameters are 2Z���jread in hierarchically, with the most general parameters first. They are also ordered according to broad ���mclasses of functionality in order to make the process of selection more intuitive. For instance all scoring-���crelated parameters are requested together. Since only the relevant parameters are requested based ���jon preceding selections, it is recommended that initial parameter selection be done interactively to gen���A7erate a sensible input file as painlessly as possible. x���!eThe following list of parameters are grouped according to the order they are requested at run time. ���A^Again, many parameters are listed here that will not be requested during your particular run. y���!eThe default values listed here may be different from those provided during a particular run, because &���AVdock tries to recommend sensible parameter values based on preceding selections. WzUTU<��@i%qv"dock input Parameters HH��ˆ�����k�b����HH��ˆ��agcc ���ff�l�����d�������l��������gg�������� HH��ˆ������ e����HH��ˆ��¢����oFg�osw{GKOSW[_cgkosw�W{&��@hqw HH��ˆ�����o�e����HH��ˆ��djff���ff�l�����d�������p��������jj�������� HH��ˆ������ h����HH��ˆ��œ�� ���GZj�GKOSW [_cgkosw��HH��ˆ�����s�h����HH��ˆ��gmii ���ff�l�����d�������t��������mm�������� HH��ˆ������ k����HH��ˆ�������nm �[_cgkosw��HH��ˆ�����w�k����HH��ˆ��jpll���ff�l�����d�������x��������pp�������� HH��ˆ������ n����HH��ˆ������op �osw#'+�W|ꪜ��@hqx HH��ˆ�����{�n����HH��ˆ��msoo ���ff�l�����d�������|��������ss�������� HH��ˆ������ q����HH��ˆ��������.s �#'+���HH��ˆ������q����HH��ˆ��pvrr���ff�l�����d���������������vv�������� HH��ˆ������ t����HH��ˆ��y������/^v ����W}��@hqy HH��ˆ������t����HH��ˆ��syuu ���ff�l�����d���������������yy�������� HH��ˆ������ w����HH��ˆ��²��� �� By ��CGKOSW[_cgkosw�W~��@hqz HH��ˆ������w����HH��ˆ��v|xx���ff�l�����d���������������||�������� HH��ˆ������ z����HH��ˆ��4�� � ��Cn|� CGKOSW[_cgkosw��HH��ˆ������z����HH��ˆ��y{{ ���ff�l�����d����������������������� HH��ˆ������ }����HH��ˆ��‹�� ��o�osw#'�W���@hq{ HH��ˆ������}����HH��ˆ��|~~���ff�l�����d����������������������� HH��ˆ������ �����HH��ˆ������ ��*�#'���HH��ˆ�����������HH��ˆ�� ���ff�l�����d����������������������� HH��ˆ������ ����HH��ˆ��������2����W���@hq| HH��ˆ����������HH��ˆ�����ff�l�����d��������������� �������� HH��ˆ����� � ����HH��ˆ��²�����+v��w{���@hq} Q��@hq~ HH��ˆ����������HH��ˆ��  ���ff�l�����d��������������� !�������� HH��ˆ������ ����HH��ˆ��¤�� ��we �w{filorux{�W��@hq HH��ˆ������ ����HH��ˆ�� ���ff�l�����d���������������"�������� HH��ˆ������ ����HH��ˆ������ ��f}�filorux{���HH��ˆ������ ����HH��ˆ��   ���ff�l�����d���������������#�������� HH��ˆ������ ����HH��ˆ��G���� ��~����W��@hq HH��ˆ����������HH��ˆ�����ff�l�����d���������������$�������� HH��ˆ������ ����HH��ˆ��� ��� ���������`  ���`Output &��� odock reports several kinds of information as output which is either written to screen in interactive mode F���@Ror written to file in batch mode. Each section of the output is discussed below.  f��@hHeadingq  c��� qThe heading lists general information about the current job. The %launch_time, %host_name and 2%n����[working_directory fields are useful to help the user archive the run conditions. The ����kmemory_limit field refers to the amount of RAM in bytes available to the job. This is can at most be "����gequal to the physical memory of the computer, but may be less if limits have been imposed on the users ����gshell. If the job requires more RAM than is available, then execution is stopped and an error message ���@ is reported. Q ���` HH��ˆ����������HH��ˆ�� ���ff�l�����d���������������%�������� HH��ˆ������ ����HH��ˆ��k� ��� ������  ��@hParametersq  ��� lAll input parameters are echoed into the output. In fact, the output file may be used as an input file for 0����hanother run. This is a useful technique to clean up an old, cluttered input file and make a tidy, well-���@organized input file.  8��� gThis particular parameter list is nearly the shortest possible since most general parameters have been C��� ~turned off. It is constructed automatically when &dock is used to convert a molecule file format (see q'Mol'���M2ecule File Conversion' on page 54q). ]��� mIf a parameter is not needed it is not reported in the output. The user can override this feature and force h���Lall parameters to be written out by using the %-v flag (see q'Command-line Arguments' on page 53q).  ��@h Resultsq N��� uThe docking results of each molecule are output as above. In terse mode (%-t flag) all results are printed Y���@on a single line. Qh���`CThis particular output is from the flexible docking of a molecule. HH��ˆ����������HH��ˆ�����ff�l�����d���������������&�������� HH��ˆ�����#� ����HH��ˆ��`���������� ��@hqPerformanceq ���,xThis section of the output is generated if the user used the %-p command-line flag (see q'Command-line '��� vArguments' on page 53q). It is intended to help the user to understand the performance bottlenecks of a "���cparticular run and to make informed parameter choices. Since minimization can consume significant ���@5portions of cpu time, it is profiled in more detail. C��� jThis particular output is from a flexible docking run in which a majority of the cpu time is spent during N���@$the peripheral conformation search. Q]���` HH��ˆ����������HH��ˆ�� ���ff�l�����d���������������'�������� HH��ˆ�����'� ����HH��ˆ��{�&���&���������` L���hqqQgrid Y���`Author: Todd Ewing d���`0Based on work by Elaine Meng and Brian Shoichet  ���` Overview &��� ugrid creates the grid files necessary for rapid score evaluation in &dock. Three types of scoring are 2����iavailable: contact, chemical and energy scoring. The scoring grids are stored in files ending in *.cnt, ����i*.chm, and *.nrg respectively. When docking, each scoring function is applied independent of the others ���@6and the results are written to separate output files. &Ԫ��� lgrid also computes a bump grid which identifies whether a ligand atom is in severe steric overlap with 2ߪ����ia receptor atom. The bump grid is identified with a *.bmp file extension. The file containing the bump ���@Ggrid also stores the size, position and grid spacing of all the grids. ��� iThe grid calculation must be performed prior to docking. The calculation can take up to 45 minutes, but 0����oneeds to be done only once for each receptor site. Since &dock can perform continuum scoring without ����ha grid, the grid calculation is not always required. However, for most docking tasks, such as when mul����gtiple binding modes for a molecule or multiple molecules are considered, it will become more time effi���@'cient to precompute the scoring grids.  E���`Bump Checking Y��� gPrior to scoring, each orientation can be processed with the bump filter to reject ones that penetrate 0d����fdeep into the receptor. Orientations that pass the bump filter are then scored and/or minimized with ���@(any of the available scoring functions.  ~��� oThe way a bump is detected has been changed from previous versions of &dock. Instead of a strict dis0����gtance cutoff, a bump is based on the sum of the van der Waals radii of the two interacting atoms. The ����huser specifies what fraction of the sum is considered a bump. For example, the default definition of a ���@Nbump is if any two atoms approach closer than 0.75 of the sum of their radii. !��� gThe way bump information is stored on a grid has also changed. Rather than storing a True/False value 0����sat every grid point, &grid stores an atomic radius which corresponds to smallest radius of ligand atom at ����kthe grid position which would still trigger a bump. During docking, for a given orientation, the position ����gof each atom is checked with the bump grid. If the radius of the atom is greater than or equal to the ����hradius stored in the bump grid, then the atom triggers a bump. To conserve disk space, the atom radius ����fis multiplied by 10 and converted to a short unsigned integer, which takes up as much memory (1 byte) ���@=as the True/False value used in the previous implementation. " ���`Energy scoring #$���,The energy scoring component of &dock is based on the implementation of force field scoring (See q'20q 0/��� in the q'Referencesq section of the q'Users Guideq) in earlier versions of &dock. Force field scores are approx���dimate molecular mechanics interaction energies, consisting of van der Waals and electrostatic compo���@nents: ]$T71eTc�� h qq HH��ˆ����������HH��ˆ�� ���ff�l�����d��������������� (�������� HH��ˆ�����+� ����HH��ˆ��F����!`s ����%��� {where each term is a double sum over ligand atoms <i and receptor atoms <j, which include the quantities ��@Hlisted below.q &���`$Generalization of the VDW component 'ߪ��� cThe van der Waals component of the scoring function has been generalized to handle any combination 0ꪚ����zof repulsive and attractive exponents (providing that =a > =b). The user may choose to "soften" the po����etential by using a 6-9 Lennard-Jones function. The general form of the van der Waals interaction be���LJtween two identical atoms is presented in q'Equation 2q, (]J�� h qq )6 ��@h9which includes the following additional quantities.q * ���`lThe coefficients =C and =D can be determined given the two following boundary conditions. +s�� hq, at q ,�tg�� hq, at q -���,{Application of these boundary conditions to q'Equation 2q yields an expression of the van der Waals inter���D3action with a generalized Lennard-Jones potential. .]Fr�� h qq /,5���,~The consequence of using a different exponent for the repulsive term are illustrated in q'Figure 1q. Notice p74���ethat the well position and depth are unchanged, but that the repulsive barrier has shrunk by about a ���@quarter Angstrom. HH��ˆ����������HH��ˆ��# ���ff�l�����d���������������##)�������� HH��ˆ�����/� !����HH��ˆ������X��#����0UTUT�� h8qqDistance dependence of Lennard-Jones Function 1���`"Precomputing potentials on a grid 2US]���,0By inspection of q'Equation 1q and q'Equation 5q, the repulsion and attraction parameters (<A?ij and <B?ij) for the UU#Z���D|interactions of identical atoms can be derived from the van der Waals radius, <R, and the well depth, @e. 3]> �� hq and q 4Yr��� hIn order to evaluate the interaction energy quickly, the van der Waals and electrostatic potentials are 0dr����hprecomputed for the receptor and stored on a grid of points containing the docking site. Precomputing ����{the van der Waals potential requires the use of a geometric mean approximation for the =A and =B terms, ���L,as shown in q'Equation 7q. 5;t\�� hqq and q 6<z���lKUsing this approximation, q'Equation 1q can be rewritten: 7TT�� h qq 8w��� pThree values are stored for every grid point <k, each a sum over receptor atoms that are within a user-w���@&defined cutoff distance of the point: 9Tb �� h&qq , q , and q :..:��� kThese values, with trilinear interpolation, are multiplied by the appropriate ligand values to give the in09.9����zteraction energy. &gridM calculates the grid values and stores them in files. The values are read in during ��� a &dockM run and used for force field scoring. Substituting q'Equation 9q into q'Equation 8q, the interaction en���D ergy is: ];Tn�� hq HH��ˆ������!����HH��ˆ�� &""���ff�l�����d���������������&&*�������� HH��ˆ�����3� $����HH��ˆ��Y����%%��&����<���`RAtoms that fall outside the grid, if any, are given interaction energies of zero. =���,The user determines the location and dimensions of the grid box using the program& q,showbox&q. It is not 0���cnecessary for the whole receptor to be enclosed; only the regions where ligand atoms may be placed ����dneed to be included. The box merely delimits the space where grid points are located, and does not ����jcause receptor atoms to be excluded from the calculation. Besides a direct specification of coordinates, ����jthere is an option to center the grid at a sphere cluster center of mass. Any combination of spacing and <���@0x, y, and <z extents may be used. > l���`Contact Scoring ?��� uContact scoring in &grid incorporates the scoring performed with the &distmap program developed by 0����cShoichet and Bodian. The score is a summation of the heavy atom contacts (every atom except hydro����dgen) between the ligand and receptor. A contact is defined as an approach of two atoms within some ����hcutoff distance (usually 4.5 Angstroms). If the two atoms approach close enough to bump (as identified ����gwith the bump grid) then the interaction can be penalized by an amount specified by the user. The dis���LVtance dependence of the contact score is represented in q'Figure 2q. @UTUG�� h8qqDistance dependence of contact score function AїP��� |Unlike the convention in &distmap, an attractive score in &grid is negative and a repulsive score is posi0ܗO����htive. This switch of sign was necessary to allow the same minimization protocol to be used for contact ���@+scoring as implemented for energy scoring. B ���`Chemical Scoring CM��� gChemical scoring is an optional scoring function which is based on energy scoring, but incorporates em0&L����jpirical concepts of molecular interaction. It includes the van der Waals and electrostatic terms from en����fergy scoring, but the attractive portion of the van der Waals term has been modified. The attractive ���@Mportion is scaled depending on the chemical nature of the interacting atoms. DKI��� fThe philosophy of chemical scoring is to give some control over scoring to the user without requiring PVH���Lany programming effort. Please see the section titled q'Chemical Score' on page 40q for more discussion. HH��ˆ������$����HH��ˆ��#)%% ���ff�l�����d���������������))+�������� HH��ˆ�����7� '����HH��ˆ��� ��� ����)����E���`Chemical labeling of atoms F��� fAtoms are identified with particular chemical labels depending on their atom type and the types of ad0��� jacent atoms. See q'chem.defn' on page 106q for an example of chemical labels and definition rules. The ���hfile containing these rules is a text file and can be modified by the user. Consequently, the user can ���@2create any set of labels and definitions desired. GP���`Scaling of interactions H`��� aThe van der Waals interaction between two atoms is scaled based on the rules contained in a user-pk��� �supplied file (see q'chem_score.tbl' on page 108q). The scaling factors provided with the distributed ver���ision of dock are merely suggestions. They are not derived from first principles, nor are they fitted to ����bexperimental data. They should be considered preliminary and can be adjusted depending on the in���@Hterests of the user and the considerations of a particular test system. HH��ˆ������'����HH��ˆ��&,((���ff�l�����d���������������,,,�������� HH��ˆ�����;� *����HH��ˆ��W������z,����I ���hqCommand-line Arguments J��@hq K&��� lgrid may be executed in either interactive or batch mode, depending on whether output is written to a 2����ifile. In interactive mode, the user is requested only for parameters relevant to the particular run and ����kdefault values are provided. This mode is recommended for the initial construction of the input file. In ����lbatch mode, input parameters are read in from the input file and all output is written to the output file. ���@NThis mode is recommended once an input file has been generated interactively. L <���`Interactive mode M%P���`grid -i grid.in N_��� yWhen launched this way, &grid will extract all relevant parameters from %grid.in (or any file supplied 0j����by the user). If additional parameters are needed (or if the %grid.in file is non-existent or empty), &grid ����dwill request them one at a time from the user. Reasonable default values are presented. Any param����teters supplied by the user will be automatically appended to the %grid.in file. If the user would like to ���@kchange any previously entered values, the user can edit in the %grid.in file using a text editor. O%���`grid -i P&���`Xgrid will behave as above, but will assume the input file to be %grid.in. Q%���`grid -s R&��� sgrid will run interactively, but will not check any input file for parameters and will not append any entered Ҫ���@parameters to a file. S ���` Batch mode T%���`grid -i grid.in -o grid.out U&��� ugrid will run in batch mode, extracting all relevant parameters from %grid.in (or any file supplied by 2 ����uthe user) and will write out all output to %grid.out (or any file supplied by the user). If any parameters ����hare missing or incorrect, then execution will halt and an appropriate error message will be reported in %���@grid.out. VE���` grid -i -o CW&���`ngrid will behave as above, but will assume the i/o files to be %grid.in and %grid.out. HH��ˆ������*����HH��ˆ��)/++ ���ff�l�����d���������������//-�������� HH��ˆ�����?� -����HH��ˆ��“� ����;/��<@DHLPTX�X ���`Input Parameters Y ���` File Format ZF���lLSee q'Table 2. on page 55q for file format specifications. [ f���` Parameters \z��� {Like &dock, &grid should be executed in interactive mode to construct an input file since not all parame0����iters need to be specified for most runs. After all parameters have been entered, use CTRL-C to kill the ���@Aprocess and resubmit it in batch mode using the same input file. ]UTUO��@h%q"grid input parameters W^ê��@hq HH��ˆ������-����HH��ˆ��,2..���ff�l�����d���������������22.�������� HH��ˆ�����C� 0����HH��ˆ��*� �����<[2 �<@DHLPTX���HH��ˆ������0����HH��ˆ��/511 ���ff�l�����d���������������55/�������� HH��ˆ�����G� 3����HH��ˆ��������\y5!����_UTUT��@iq `UG��@iq a ���aOutput b���!yThe output of &grid contains several types of information. Like &dock, it outputs general information p���jabout the current job and echoes the parameters selected from the input file. In addition, it reports in���A,formation about the receptor and the grids. HH��ˆ������3����HH��ˆ��2844���ff�l�����d���������������880�������� HH��ˆ�����K� 6����HH��ˆ��g� ��� ��8"����c ��@iReceptor informationq d���!pThis portion of the output lists any merged cap residues. The cap residues are introduced by &sybyl. 0)���fCharged residues are also listed. If any residues have a non-integer charge, then either the charges ���gwere not properly loaded into the receptor input file, or some atoms are missing from the input file. ���EOThese problems should be resolved before continuing with the grid calculation. eN���%{To display more information about parameters that &grid assigns to the receptor, use the %-v option (see Y���M=q'Command-line Arguments' on page 79q). f y��@iGrid Informationq g4���!eInformation about the grid geometry is reported. The total number of grid points can be adjusted by 0?���fchanging the input box dimensions or changing the grid spacing. Generally a value under 1 million is ���A3appropriate, but this depends on system resources. hY���!iThe progress of the calculation is reported as the percent of protein atoms processed. This calculation Pd���AUusually takes up to 30 minutes depending on the grid geometry and the receptor size. HH��ˆ������6����HH��ˆ��5;77 ���ff�l�����d���������������;;1�������� HH��ˆ�����O� 9����HH��ˆ��v�)���)����;#����i���` jQ���hqqsphgen kY��`Author:Irwin D. Kuntz lh��`0Modified by:Renee DesJarlais, Brian Shoichet m ���` Overview n&���(psphgen generates sets of overlapping spheres to describe the shape of a molecule or qmolecular surface 2����(Kuntz <et al., 1982; DesJarlais <et al.,1988). For receptors, a negative image of the surface invaginations ����gis created; for a ligand, the program creates a positive image of the entire molecule. Spheres are con��� structed using the molecular surface described by Richards (1977) calculated with the program qq'msqM ���e(Connolly, 1983a, 1983b). Each sphere touches the molecular surface at two points and has its radius ����jalong the surface normal of one of the points. For the receptor, each sphere center is outside the sur����jface, and lies in the direction of a surface normal vector. For a ligand, each sphere center is inside ����hthe surface, and lies in the direction of a reversed surface normal vector. Spheres are calculated over ����dthe entire surface, producing approximately one sphere per surface point. This very dense represen����itation is then filtered to keep only the largest sphere associated with each receptor surface atom. The ����ifiltered set is then clustered on the basis of radial overlap between the spheres using a single linkage ����ealgorithm. This creates a negative image of the receptor surface, where each invagination is charac����hterized by a set of overlapping spheres. These sets, or clusters, are sorted according to numbers of ����hconstituent spheres, and written out in order of descending size. The largest cluster is typically the ��� xligand binding site of the receptor molecule. The program q'showsphereq writes out sphere center coor���DQdinates in Mpdb format and may be helpful for visualizing the clusters. o a���`Input pu���(sThe input file names and parameters are read from a file called qINSPH, which should not contain any ���@ blank lines: q���` r��`parameterformatexample s<��`msfilA802ptc.ms t��`srftpA1R u��`!dentagA1X v��`dotlimF0.0 w��`"radmaxF4.0 x��`"radminF1.4 y��`outflA802ptc.clus z���` {<��� |msfil is the name of the file containing the molecular surface calculated using the program NmsM and must 0���@Oinclude surface normals. &sphgen expects the FortranM format |?��`4(A3, I5, X, A4, X, 2F8.3, F9.3, X, A3, 7X, 3F7.3). }��� yThis format is quite different from the NqcpeM molecular surface file format. For more details, see the docY���LNumentation for q'reformatmsq and q'autoMSq. ~<h��� surftp indicates whether the spheres should lie outside the surface, as for a receptor (R or r), or inRs���@Aside the surface, as for a ligand (L or l). HH��ˆ������9����HH��ˆ��8>::���ff�l�����d���������������>>2�������� HH��ˆ�����S� <����HH��ˆ��†�2���2����>$����<���!mdentag allows the user to specify that a subset of the surface points are to be used in calculating the 2���|spheres. This density tag may be set to the values 1, 4, 9, or 0, indicating that only points having ���o1, 4, 9, or 0, respectively, in column 42 of the molecular surface file will be used; alternatively, the value ���X or x indicates that all points will be used. It is recommended that X be used unless the system is par"���mticularly large (>75,000 surface points). It is most efficient to use a partial molecular surface (if it is ���dknown in advance which region is of interest) as the calculation time scales approximately with the ���A square of the number of points. �<W���!odotlim is used to prevent the generation of large spheres whose points of surface contact are quite close 2b��� together. Each pair of points <i and <j are examined as potential sphere-defining points. <dotlim is the low��� er limit on the dot product of the vector from <i to <j and the vector from the sphere center to <j for points ���wdefining a sphere. <dotlim is typically set to 0.0, although possible values range from 1.0 to 1.0; negative ���AVvalues, however, may be useful for flat sites such as the major groove of B-form DNA. <���!sradmax is the maximum sphere radius in Angstroms. Spheres with radii larger than <radmax are discard2���red. This is important for the clustering done within &sphgen, where clusters are defined as sets of over���klapping spheres. Decreasing <radmax decreases the cluster sizes by eliminating large connector ���ispheres. In general, values from 4.0 to 5.0 Angstroms are used; values of 0.0 or less default to 5.0 Ang���Astroms. <ͪ���!tradmin is the minimum sphere radius in Angstroms. Spheres with radii smaller than <radmin are discard2ت���ced. This should be unnecessary because the molecular surface should not produce spheres of radius ���uless than the probe radius. However, some versions of NmsM occasionally place surface points very close ���ytogether. This can result in &sphgenM generating very small spheres which are not useful in characterizing ���mthe shape of the active site. It is generally advisable to keep spheres with radii equal to the probe radius ���w(typically 1.4 or 1.5 Angstroms). Note that <radmin can be set to 0.0 to allow the use of the extra radius ���A8surface developed by David Barry (unpublished results). <���aToutfil is the name of the file to which the clustered spheres will be written.  >���aOutput R���!qSome informative messages are written to a file called Routsph. This includes the parameters and files 0]���uused in the calculation. The spheres themselves are written to <outfil. They are arranged in clusters with ���ithe cluster having the largest number of spheres appearing first. The sphere cluster file consists of a ���AIheader followed by a series of sphere clusters. The header is the line N���a DOCK 3.5 receptor_spheres ���!rfollowed by a color table. The color table contains color names (format A30) each on a separate line. 0���rAs &sphgen produces no colors, the color table is simply absent. The sphere clusters themselves follow, ���A#each of which starts with the line ���a3cluster n number of spheres in cluster i  ���!|where n is the cluster number for that sphere cluster, and i is the number of spheres in that cluster. Ъ���A;Next, all spheres in that cluster are listed in the format  ߪ���a(I5, 3F10.5, F8.3, I5, I2, I3)  ���a.where the values correspond to, respectively,  ���aiThe number of the atom with which surface point <i (used to generate the sphere) is associated.  ���aGThe <x, y, and <z coordinates of the sphere center. ���aThe sphere radius. ���!jThe number of the atom with which surface point <j (second point used to generate the sphere) is 5���A associated. D���a3The critical cluster to which this sphere belongs. ���!kThe sphere color. The color is simply an index into the color table that was specified in the header. So ^}���Ap1 corresponds to the first color in the header, 2 for the second, <etc. 0 corresponds to unlabeled. m|���!jThe clusters are listed in numerical order from largest cluster found to the smallest. At the end of the px{���vclusters is cluster number 0. This is not an actual sphere cluster, but a list of <all of the spheres gener���~ated whose radii were larger than the minimum radius, <before the filtering heuristics (<i.e. allowing only HH��ˆ������<����HH��ˆ��;A== ���ff�l�����d���������������AA3�������� HH��ˆ�����W� ?����HH��ˆ��p� ��� ����A%�������aone sphere per atom and using a maximum radius cutoff) and clustering were performed. Cluster 0 0���hmay be useful as a starting point for users who want to explore a wider range of possible clusters than ��� is provided by the standard &sphgenM clustering routine. The program qq'clusterq takes the full sphere de���kscription as input, and allows the user to explore different sphere descriptions of the site. This is par��� ticularly useful for q)Macromolecular Dockingq; it is often inefficient to use spheres that fill the entire volume ���hof the ligand macromolecule. In addition, only a portion of a cavity in the receptor macromolecule ���vmay be of interest for docking purposes. If the standard clustered output from &sphgenS provides a satis���M~factory description of the ligand molecule or receptor site, running q'clusterqM is not necessary. b���!|The program creates three temporary files: temp1.ms, temp2.sph, and temp3.atc. These are used Pm���ATinternally by &sphgen, and are deleted upon completion of the computation. HH��ˆ������?����HH��ˆ��>D@@���ff�l�����d���������������DD4�������� HH��ˆ�����[� B����HH��ˆ��R�!���!����D&�������`  ���` Accessories Te���h qaddprh z��`Author:Andrew Leach &��� oaddprh is used to add hydrogens atoms to proteins. Either PDB or &amber atom names can be speci2����ified. Hydrogens are added in favorable geometries, but this does not take into account intramolecular ����chydrogen bonding. Hydrogens are also added to waters; to add some variety into the orientation of ����ethese hydrogens, a random orientation about the three euler angles is performed before adding the hy���@ drogens. Tઢ���hqqautoMS ��`$Author:Andy Good, Daniel Gschwend &���,autoMS is an extremely useful tool for setting up for q'sphgenq. This script converts PDB files to QCPE ���ums input format, runs a QCPE &ms surface calculation, converts the resulting surface to UCSF MS format ��� with q'reformatmsq, creates a SYBYL dot file of the surface (if q'ms2dotq is available), and prepares an IN"��� |SPH file for running &sphgen. The requirements are only two files: a receptor PDB file, and an qex����qclude.pdb file. The exclude.pdb file is a subset of the receptor and contains the residues which ����tshould not be surfaced in the &ms calculation. This file can be created in several ways. The easiest, if &����psybyl is available, is to select all residues in the receptor within some radius of a known ligand, invert "����pthe selection, and write out the file in Brookhaven format as exclude.pdb. One alternative that does ��� not require &sybyl is to use q'get_near_resq to locate all receptor atoms or residues within a specified ra���L`dius of a known ligand and invert the resulting pdb file using q'invertPDBq. v���`QUsage: %autoMS Vreceptor_PDB_file [surface_density] [probe_radius] ��� pwhere Vsurface_density and Vprobe_radius are optional, defaulting to 3.0 dots/2 and 1.4, re0�����spectively. Note: before using the first time, the directory specification for the &dock hierarchy must be ���@,updated inside the &autoMS script. Tƪ���h qcharge ۪��`Author:Daniel Gschwend  &ꪐ��� tcharge is a simple &nawk script which provides residue composition for a protein, including number of 2��� zcharged residues and total charge. q'gridqs output should agree with the value generated from this pro���Dgram. !���`!Usage: charge Vpdbfile "T:���hqchemprop W#O��`Author:Renee DesJarlais HH��ˆ������B����HH��ˆ��AGCC ���ff�l�����d���������������GG5�������� HH��ˆ�����_� E����HH��ˆ��cG�+���+��G'����$ ���` Overview %��� vThe interactive program &chempropM is designed to aid the user in examining the properties of a receptor 0����qin the vicinity of a small molecule that has been oriented using &dock. The program takes as input a re����jceptor coordinate file, a file containing the coordinates of one or more ligands, and several parameters, ����fdescribed below, depending on the option chosen. There are two options: electrostatics and hydrogen ���@ bonding. &Z��� lIn the electrostatic option, the electrostatic potential from the receptor is calculated at each ligand molUSe����ecule atom center. The electrostatic potential at the position of ligand atom <j, <e?j, is calculated using UMr����equation 1, where <q?i is the partial charge on the receptor atom <i, <D is the dielectric constant, and <rWij is UU���@9the distance between atoms <i and <j: 'TTr� hq (��� lOnly the receptor atoms contribute to the value of the electrostatic potential. The partial atomic charges 0ɾ����used are those from the &amberM united-atom force field (Weiner, <et al., 1984). Only standard amino acid ����aresidues can be accommodated by this program. The receptor file must include the hydrogen atoms ����rattached to nitrogens, hydroxyl oxygens, and sulfurs, and the lone pairs on the sulfurs. A new Mpdb-for����mmat coordinate file is written out for the ligand molecules, where the electrostatic potential is printed in ����dthe temperature factor column. The molecules can then be displayed using a molecular graphics pack���@6age and colored according to electrostatic potential. ) ��� eThe hydrogen bond option helps the user identify places on the ligands where it might be appropriate 0 ����eto design in a group capable of hydrogen bonding to the receptor. Potential hydrogen bond positions ����kare identified as any ligand atom within a user-specified distance of a receptor nitrogen or oxygen atom. ����dThis option was intended mainly for use with ligand heavy atom (nonhydrogen) coordinates only. Two ����lfiles are output: a coordinate file, and a file listing the potential hydrogen bonds for each ligand in the ����winput file. In the coordinate file, each potential hydrogen bond is written in Mpdb format as a residue with ����jtwo atoms. One atom is located at the receptor nitrogen or oxygen and the other is located at the ligand ����latom. The residues are separated by Mter cards. The residue and atom names depend on the protein ����atom. The residue is named Racc if the protein atom is a carbonyl oxygen, RdnrM if the protein atom is an ����qamide or amine nitrogen, and doa if the protein atom is a hydroxyl oxygen or a histidine side chain ni���� trogen. The receptor and ligand atoms in an Racc residue are named Ra and Rd, respectively; in a Rdnr ���� residue they are named Rd and Ra, respectively; and in a RdoaN residue they are named Re1M and Re2, respec����itively. Viewing these possible hydrogen bonds with the receptor and ligand is useful for design purposes ���@Nand assessing whether the angles are consistent with strong hydrogen bonding. * Q���`Usage +ҽ��� eThe input file names and parameters can be entered interactively. Interactive use is reasonable when 0ݽ����dfewer than about 30 ligands are to be examined. The user is prompted for the names of the receptor ����mand ligand files and the type of calculation (electrostatic potential or hydrogen bond). If an electrostatic ����gpotential calculation is being performed, the user must select a constant or distance-dependent dielec����ltric, a cutoff distance, and a name for the output file. If a hydrogen bond calculation is being performed, ����hthe user must enter a cutoff distance for hydrogen bonds and names for the output files. Finally, after ����hperforming one calculation, the user is given the option of performing another without exiting from the ���@ program. ,TJ���hqr�cluster W-_��`)Authors:Brian Shoichet, Irwin D. Kuntz HH��ˆ������E����HH��ˆ��DJFF���ff�l�����d���������������JJ6�������� HH��ˆ�����c� H����HH��ˆ��€�.���.����J(����. ���a Overview /&���!tcluster allows greater flexibility in creating a sphere description of a site or molecule. It is particularly 2��� �useful in macromolecular docking, and in general, when the original cluster file from rr'sphgenr does not ���E6adequately describe the site or molecule of interest. 0D���!The &cluster program is a more elaborate version of the cluster subroutine in &sphgen (Kuntz <et al., 0O���h1982). A single-linkage clustering algorithm is applied, based on the radial overlap between spheres. ���{Unlike &sphgen, &cluster does not heuristically remove spheres; it can operate on the total set of possi���ible spheres rather than just the largest sphere per surface atom. This complete description is contained ���rin the cluster 0 from &sphgen. User-defined criteria control the clustering process; clusters can be tai���mlored to a certain size (number of spheres), a certain range of sphere radii, or a certain region of space. ���AbThe program allows one to try different clustering parameters without rerunning &sphgen. 1 ���aInput 2���!gThe program can be run either interactively or from a command file. The following is an explanation of Ū���APa sample command file. These command files should not contain any blank lines. 3/Ԫ��a$parameterX/formatexample 4<��a$clufilA802ptc.all 5��anclusI1 6��a"maxradF5.0 7��a"m2xradF5.0 8��a#povlapF10.0 9��aclusizI60 :��aminsizI20 ;��aminflgI1 <��a-outfilA802ptc.all.rcl =��aynA1 y >���a4 (if <yn is y or Y): ?<��aminradF1.3 @��arincrF0.2 A��anearnbF0.5 B��anearadF0.25 C���a D���aMclufil  is the file containing the input spheres from &sphgen. E���!ynclus is the number of the cluster to recluster (there is generally more than one in the original &sphgen 2���ucluster file). When the full set of spheres is being used, there is only one cluster and <nclus should be ���A set to 0. F<���!lmaxrad is the primary maximum sphere radius for clustering, in Angstroms. Only spheres with radii less 2���nthan or equal to <maxrad can be used as linkers between groups of spheres, making them into a single ���olarger cluster. Values from 2.5 to 5.0 Angstroms are generally most useful. <maxrad also defines the ���AZend point for analytical clustering (see below); it is the final value of <rcut. G<7���!fm2xrad is the secondary maximum sphere radius for clustering, in Angstroms. This variable allows 2B���sspheres with radii larger than <maxrad to be included in clusters, but does not allow them to act as link���ers. <m2xrad must be equal to or greater than <maxrad; smaller values default to <maxrad. All spheres ex��� ceeding the <m2xrad criterion will be discarded. <m2xrad is typically set to <maxrad for analytical clustering ���Aand 5.0 Angstroms otherwise. H<r���!opovlap is the percent radial overlap between two spheres necessary to define a pair. If this variable is R}���fset to 0.0, spheres will be defined as overlapping when they intersect to any degree. The larger the HH��ˆ������H����HH��ˆ��GMII ���ff�l�����d���������������MM7�������� HH��ˆ�����g� K����HH��ˆ��€�.���.����M)����H����tvalue of <povlap, the greater the overlap necessary to define the spheres as a pair for cluster purposes. ���@'Typical values range from 0.0 to 20.0. I<��� mclusiz is the maximum number of spheres allowed to be in a cluster. Growth of a cluster is frozen when 2����gthis limit is reached; spheres that would otherwise be added are discarded. Limiting the cluster size ����fleads to decreased coalescence and therefore greater numbers of clusters. Values of 50 to 75 are sug���@gested. J<P��� uminsiz is the minimum number of spheres a cluster must have to be included in the output. <minsiz must [���@Bbe less than <clusiz; values of 20 to 30 are suggested. K<j��� mminflg is the minimum number of flagged spheres a cluster must have to be included in the output. Flag2u����iging is done by placing any non-blank characters following the information for the sphere(s) of interest ���@Gin <clufil. YThe flagging feature is no longer supported. L<��� syn indicates whether analytical clustering will be done. Analytical clustering refers to iteratively increas2����iing the value of the primary maximum sphere radius. It is especially useful when the input sphere set is ���� large (>1000, as when the full sphere description is being used). If <yn equals N or n, analytical clustering ����swill not be done, and no further input is read. Analytical clustering replaces <maxrad with the variable <����rcut, which increases from <minrad to <maxrad in step sizes of <rincr. Each value of <rcut corresponds to a "����kcycle of clustering. In this way, the user can quickly determine which parameters will yield a cluster of ����hthe desired size. For a set of 1000 spheres, a typical analytical run with averaging takes about 20 sec����monds on a Silicon Graphics Iris 4D/25 workstation. Most of the Mcpu time is spent in averaging the ���@bspheres; for this reason, run time scales approximately with the square of the number of spheres. M<���`Ominrad is the starting value for <rcut in analytical clustering. N���`arincr is the incremental increase in <rcut per iteration in analytical clustering. O��� fnearnb is the maximum distance between the centers of spheres that may be averaged into a compos2����kite sphere, for analytical clustering. This variable is used to simplify very large sets of spheres. When ����iclusters are written out, only the sphere closest to the composite will be included. A value of 0.5 Ang���@=stroms is reasonable for sets of approximately 1000 spheres. P<D��� jnearad is the maximum difference in magnitude between the radii of spheres that may be averaged into 2O����fa composite sphere, for analytical clustering. A value of 0.25 Angstroms is reasonable for sets of ap���@proximately 1000 spheres. Q z���`Output R��� kFor analytical clustering, the output sphere cluster file consists of several sphere cluster files concate0����qnated together. Each group begins with its own header (dock 3.5 receptor_spheres, <etc.). The ���@Duser must hand-edit this file to select the best group of clusters. STϪ���h rcolsph T䪉��`Author:Mike Connolly U&��� ncolsph reads and writes a sphere cluster file, adding a color (label) table and sphere labels. The color 2����jis determined by evaluating either a Delphi map or a force-field grid at the sphere center, and comparing ����tthat value to the ranges specified in a user-defined <range file, which defines ranges for a series of col���@8ors. The program prompts for the information it needs: V#���`/scoring map type (2 = Delphi, 3 = force-field) W���`8the Delphi map file name or the force-field grid prefix X���`range file name Y���`input sphere cluster file name Z���` output sphere cluster file name [���`QThe range file is the only one that needs explanation. Its format is as follows: C\%���`color_name range_min range_max HH��ˆ������K����HH��ˆ��JPLL���ff�l�����d���������������PP8�������� HH��ˆ�����k� N����HH��ˆ��ƒ�%���%����P*����]��� hThe spacing between the values does not matter. The %color_name can be up to 30 characters in 0����~length. The %range_min and %range_max must be <real numbers, and specify the lower and upper ends ���@Uof the range respectively. There may be up to 100 colors and 200 range statements. ^TG���hrrcondense _\��`Author:Daniel Gschwend `&k���,condense takes as input a residue list generated by r'get_near_resr and compacts it into a format suitable 2v��� &for an &ms -i file (for the UCSF version of &ms - for the QCPE &ms version, see r 'autoMSr ). This functionality ���mcomes in handy when attempting to generate an &ms surface for a portion of a receptor. The program ��� ~r 'get_near_resr  can be used to obtain a listing of all receptor atoms within a specified distance of a small ���}molecule, <e.g. a crystallographically observed ligand. &condense will then reformat and compact the list���ning to less than 100 entries for compatibility with UCSF &ms. This program supports command-line op���D3eration: type condense -h for details. aTت���h r conect b��`Author:Elaine Meng c&��� conectM is an interactive program that appends Mconect records to a Mpdb file containing the coordinates 2����hof a single molecule. The user is prompted for the names of the input and output files. The presence of ����da bond is determined as follows: two atoms are bonded if the distance between them is less than or ���@Qequal to the sum of their covalent bond radii plus a tolerance of 0.4 Angstroms. dTH���h rconvsyb e]��`Author:Elaine Meng fl���,The interactive program &convsybM converts r'SYBYL MOL2 formatr files into a number of other formats w���|useful for &dockM and some of the accessory programs. Output options include extended Mpdb format, &����dockM 3.0 database format, and standard Mpdb format. &convsybM assumes that each M@<tripos>moleM����jcule record type indicator corresponds to a single covalently bonded structure, and uses the first 9 "����wcharacters of the line following this record as the refcode for the structure. Multi-Mmol2 files are handled ���@ correctly. gTΪ���hrfdat2pdb h㪏��`Author:Daniel Gschwend i���,�Converts a r'Cambridge Crystallographic Databaser FDAT file (as from a search with &quest) to PDB for���DGmat. Multiple structures in the same FDAT file are handled correctly. j ��� xUsage: fdat2pdb Vcambridge_prefix (an input file called Vcambridge_prefix.fdat is expected, ���@Mand output file called Vcambridge_prefix.pdb will be created). kTB���hrrget_near_res lW��`Author:Daniel Gschwend mf���`SGiven a ligand PDB file and a receptor PDB file, performs either of two functions: n��� Writes a PDBM file containing all atoms of all residues in the receptor which have their C@a atoms within P€����ya specified distance of the ligand. A list file is also written which gives the closest C@a-to-ligand distance HH��ˆ������N����HH��ˆ��MSOO ���ff�l�����d���������������SS9�������� HH��ˆ�����o� Q����HH��ˆ��{�+���+����S+����n���@for each residue written. o��� xWrites a PDBM file containing all atoms of all residues in the receptor which have any atom within a 0����pspecified distance of the ligand. A list file is also written which gives the closest receptor-ligand distance ���@for each residue written. p���,The list file output may be converted to an UCSF &msM -i file with the r'condenser program. This utility can 0E��� also be used with the r'autoMSr program using QCPE &ms surfaces: to generate an exclude.pdb file ���LGfrom &get_near_res output, see r'invertPDBr. qT{���h rhbdata r��`Author:Andy Good s���,|This program automatically runs r'Goodfords 'gridr program (version 11.01, distributed independently; 0���sGoodford, 1985) for a variety of probes, creating &sybyl contour files and files containing centers of fa��� vorable interaction energy for r'sphgenr  file creation. It also runs &grin and will stop if &grin encounters a ���{problem with the Mpdb file. The program requires an input file called Rhbin which should follow this ex���@ample: tڪ���` u��`U3dfrname of parent protein (Mpdb file name - used for file naming) v��`0/bert/grid11.01root directory for GRID w��`--12.0minimum <x coordinate x��`,26.0minimum <y coordinate y��`+4.0minimum <z coordinate z��`+9.0maximum <x coordinate {��`,48.0maximum <y coordinate |��`,33.0maximum <z coordinate }��`O1.0grid density - # of planes per Angstrom of NgridM map ~��`R-7.0highest permitted interaction energy included in site point creation ��`U1.0exclusion sphere to remove local low energy pts. near each local minimum ���`^2# of probes in probe list that will be used - first two are N3+, O:: ���` ���,Notes for use in conjunction with r!'mol2sphr": The &gridM energy of each point is assigned to the charge 0���gfield for reference purposes and atom types are set to dummy. Both of these fields must be corrected, ��� the &sphgen file converted into Mpdb format using r#'showspherer$, the resulting atom types modified and ��� combined within &sybyl before they can be written to MOL2M format in preparation for r%'mol2sphr& conver���Dsion. T���hr'r(idtosyb ��`Author:Elaine Meng '���,This program is designed to be used in combination with &sybyl to convert Mpdb files into r)'SYBYL MOL2 '2��� formatr* files. Do not use it by itself. The generated &mol2 files are incomplete. First run &idtosyb on the &����pdb file, then read the generated &mol2 file into &sybyl to verify the atom types, add hydrogens, and as"����psign partial charges. &sybyl does a less than satisfactory job of assigning atom types and bonds when ����yreading in small molecule Mpdb files. &idtosyb uses bond length data from the Cambridge Structural Da����jtabase to assign atom types in a far superior fashion, although still not perfect. Hydrogens need not be ���@opresent in the input, and multiple ligands in the same file are processed if separated by Mter cards. Qx���lKUsage: see r+'pdb2sybr,, a front-end to &idtosyb. HH��ˆ������Q����HH��ˆ��PVRR���ff�l�����d����������������VV:�������� HH��ˆ�����s� T����HH��ˆ��\�$���$����V,����T���hr-r.invertPDB ��`Author:Daniel Gschwend  ��� A shell script to extract all atoms in a larger Mpdb file which are not in a smaller Mpdb file, where the latter 0����vis a subset of the former. For example, after acquiring a Mpdb file of all protein atoms or residues within ��� a specified radius of a known ligand with r/'get_near_resr0, the inverse atoms (<i.e. those far away from the ���L ligand) may be selected to generate an exclude.pdb file for use with r1'pdb2msr2 or r3'autoMSr4.  b���`[Usage: invertPDB Vlarger_PDB_file smaller_PDB_file > Vinverted_PDB_file  T���hr5r6mol2sph  ��`Author:Andy Good  ���, Takes r7'SYBYL MOL2 formatr8 files and converts them into r9'sphgenr: format files, allowing automatic color0���ving of the receptor. Currently, N.3 atoms are classed as H-bond donors, O.3 as H-bond acceptors, ����oand S.3 as hydrophobes, but these color setting can be changed to user preferences by simply hacking ����kthe file. The charge value can also be used to assign critical clusters, with the critical cluster number ���@,equal to the truncated value of the charge. T���hr;r<ms2dot ��`Author:Andy Good &,��� ms2dot converts UCSF &ms surface files into &sybyl dot files. This allows visualization in &sybyl of the 7��� surface created for use with r='sphgenr>. <Note: this program is not installed by default, as it requires &sybyl< <���sprogramming libraries for compilation. To install this program you must explicitly compile it with make ����zms2dot in the accessories source directory, provided you have &sybyl libraries installed. Please ���@Xread the Makefile in the accessories directory for further details. T���hr?oldscore ��`Author:Elaine Meng &��� �oldscoreM is an interactive program that allows scoring of &dockM output according to the old, exponen2����wtial algorithm (as in version 1.1; DesJarlais <et al., 1988). The user is interactively asked for the names ����of the receptor file, the ligand file, and a file for output, plus the values of <concut, <dmin, and <discut. There ����tmay be many ligands in the ligand file, as long as each ends with a Mter card. Bad contacts are counted. ����uThere are slight differences in the scores directly from &dockM 1.1 and the scores reported by this pro����fgram, because the coordinates of ligand orientations are rounded to three decimal places when written ���@out. T���hr@rApdb2ms )��`Author:Andy Good 8��� rThis program is used to create input files for QCPE &ms from standard PDB files. The receptor file must pC����qbe called fort.1; the residues of the receptor which should be included in the surface calculation but ����znot have a surface drawn should be placed in a file called fort.2; output is written to fort.3. This ���LHprogram is part of the automated process of rB'autoMSrC. HH��ˆ������T����HH��ˆ��SYUU ���ff�l�����d���������������YY;�������� HH��ˆ�����w� W����HH��ˆ��„�"���"����Y-����T���hrDrEpdb2syb ��`Author:Daniel Gschwend ���,This program is a front-end to rF'idtosybrG. Please read the description of &idtosyb before using this pro���Dgram. L���`#Usage:  pdb2syb VPDB_file ���`sNote: before using the first time, update the pathnames inside the script for location of &idtosyb. T���hrHpdbrenum ��`Author:Daniel Gschwend &��� kpdbrenum is a versatile residue and atom renumbering utility. It provides many features with respect 2����hto where to start numbering, how to treat separate molecules, and also supports individual treatment of ����ywater molecules, including their separation by Mter cards for easier visualization. &pdbrenum also at����itempts to update Mconect records when atoms are renumbered. This program supports command-line ���@4operation: type pdbrenum -h for details. T���hrIpdbtosph  ��`Author:Elaine Meng !&%���` pdbtosph makes a sphere cluster file out of the non-hydrogen Matom records (not Mhetatm) in a Mpdb file. "TP���hrJptrentry #e��`Author:Todd Ewing $&t���,�ptrentry is a self-running nawk script which extracts selected molecule entries from a rK'PTR formatrL file 2���eand displays the data for each molecule in a readable format. A single molecule, or a range of mole���@cules, may be selected. %��`CTo extract the first molecule, type:%ptrentry file.ptr 1 &��`JTo extract the first 10 molecules, type:%ptrentry file.ptr 1 10 'TӪ���hrMptrfield (誒��`Author:Todd Ewing )&���,ptrfield is a self-running nawk script which extracts selected fields from a rN'PTR formatrO file. It is useful ���Dlto shuffle the field order in a file to make sorting sorting easy. This would be accomplished as follows: *%���`?ptrfield file.ptr NRG FILE FPOS END | sort +1n > file_sort.ptr +T<���h rPqcpe_ms ,Q��`Author:Mike Connolly -`���,rQ'sphgenrR requires that a molecular surface be calculated and that it be converted to the UCSF &ms format pk��� using rS'reformatmsrT. &qcpe_ms is distributed only as a tool for the rU'autoMSrV script. You should contact ��� QCPE directly for obtaining the complete software package for &ms (#429) - see rW'Sources' on page 112rX ���Dfor contact information. HH��ˆ������W����HH��ˆ��V\XX���ff�l�����d���������������\\<�������� HH��ˆ�����{� Z����HH��ˆ���)���)����\.����.T���hrYrZreformatms /��`Author:Renee DesJarlais 0&���,/reformatmsM converts an &msM file of Nqcpe format to an &msM file of the format read by r['sphgenr\. &reformat���msM requires a Brookhaven Protein Data Bank coordinate file as well as the QCPEN &ms file as input. The ���Dprogram is interactive. 1W��� �The Nqcpe &ms file must be in the long format: The FortranM format for this file and the information conb���@tained in it are listed below: 2q���` 3��`#(3I5, I2, 3F9.3, 4F7.3, I2) 4���` 5��`<<n1, n2, n3, shape, x, y, z, area, xn, yn, zn, buried 6���` 7��`K<n1atom number of atom that surface point is on or closest to 8��`=<n2other atom that probe touches (0 for convex) 9��`c<n3third atom that probe touches, <n3><n2 (0 for convex and saddle) :��`4<shape1: convex, 2: saddle, 3: concave ;��`2<x, y, zcoordinates of surface point <��`*<areasolvent-accessible area =��`=<xn, yn, zncomponents of the unit vector normal >��`A<buried0: exposed, 1: buried, blank: not determined ?���` @��`,The lines must be sorted by <n1. A���` B���` C���`pThe NmsM format that &sphgen reads and the information that it contains are listed below: D���` E��`-(A3, I5, 2X, A3, 3(F8.3, X), X, A3, 4F7.3) F���` G��`7resnm, nres, atnm, x, y, z, srftag, area, xn, yn, zn H���` I��`l<resnmresidue name of the closest atom, or the atom itself (if <srftag = A) J��`m<nresresidue number of the closest atom, or the atom itself (if <srftag = A) K��`c<atnmname of the closest atom, or the atom itself (if <srftag = A) L��`6<x, y, zcoordinates of the point or atom M��`�<srftagA: atom, RSR0: reentrant point, SS0: saddle point, SC0: convex point N��`T<areasolvent-accessible area (blank if <srftag = A) O��`g<xn, yn, zncomponents of the unit vector normal (blank if <srftag = A) PTO���h r]rmsd Qd��`Author:Daniel Gschwend Rs��� nCalculates root mean squared deviation in Angstroms per atom for two Mpdb files. Treatment of hydroP~����mgens is optional. Also, one may compare two files side by side, or use the first molecule in the first file HH��ˆ����� �Z����HH��ˆ��Y_[[ ���ff�l�����d������� ��������__=�������� HH��ˆ������ ]����HH��ˆ��b�*���*����_/����R����has a reference for all molecules in the second file. All atoms must be in identical order and have the ����fsame atom names for both input files. This program supports command-line operation: type rmsd -���@h for details. STG���h%r^r_r`sdf2mol2 & rasybdb T\��`Author:Daniel Gschwend Uk��� cAs an interface to the commonly used databases from Molecular Design Limited, we are providing two v���Luconversion schemes to convert SD files (such as from &isis) to rb'SYBYL MOL2 formatrc files. V��� bThe conversion scheme described here was developed to be easy to use and accurate in its atom-typ0����ging and partial charge computation. Although still an area of active development, it has to date been ���@/tested visually on several thousand compounds. W��� wThis scheme consists of two programs run sequentially, &sdf2mol2 is written in Fortran and &sybdb in &����nsybyl's programming language, &spl. Taken together, one can convert an MDL SDF-format database "����uinto a &sybyl MOL2 format database which has appropriate &sybyl atom types assigned, hydrogens add����ged, and partial charges computed. To find out more about the conversion process, including how to use ����~it, please consult the 00README file in the directory ./source/database/sdf2mol2 under the &dock ���@root. X/��� pNote: The second phase conversion requires &sybyl for hydrogen addition and charge computation. 2����vThe former program, &sdf2mol2, may still be of some use to users who do not have &sybyl but have mo����olecular modeling packages than can read MOL2 format (e.g. &insight). Hydrogen addition, substructure ����_removal, and charge computation must then be performed within the context of your own modeling ���@ package. YTG���hrdreshowbox Z\��`Author:Elaine Meng [&k��� vshowboxM is an interactive program that allows visualization of the location and size of the grids that will 2v��� be calculated by the program rf'gridrg, using any graphics program that can display Mpdb format. The user is ���jasked whether the box should be automatically constructed to enclose all of the spheres in a cluster. If ���eso, the user must also enter a value for how closely the box faces may approach a sphere center (how ����hlarge a cushion of space is desired) and the sphere cluster filename and number. If not, the user is ����easked whether the box will be centered on manually entered coordinates or a sphere cluster center of ����cmass. Depending on the response, the coordinates of the center or the sphere cluster filename and ����fnumber are requested. Finally, the user must enter the desired box dimensions (if not automatic) and ���@5a name for the output Mpdb-format box file. \T���hrhrishowsphere ]��`6Authors:Stuart Oatley, Elaine Meng, Daniel Gschwend ^&��� showsphereM is an interactive program; it produces a Mpdb-format file of sphere centers and an Nms-like ����pfile of sphere surfaces, given the sphere cluster file and cluster number. The surface file is not in Nqcpe &��� msM format (see the documentation on rj'reformatms' on page 95rk for further details); generation is optional. "���iThe user may specify one cluster or all, and multiple output files will be generated, with the cluster ��� znumber appended to the end of the name of each file. The input cluster file is created using rl'sphgenrm. &���nshowsphereM requests the name of the sphere cluster file, the number of the cluster of interest, and b����gnames for the output files. Information is sent to the screen while the spheres are being read in, and ���@/while the surface points are being calculated. HH��ˆ������]����HH��ˆ��\b^^���ff�l�����d���������������bb>�������� HH��ˆ������ `����HH��ˆ��K��������b0����_T���hrnsplitmol `��`Author:Daniel Gschwend a��� A full-featured structure file splitting utility which accepts either Mpdb or &sybyl Mmol2 format files. A range p����eof molecules can be extracted from the input, and a user-specifiable number of molecules is put into ���@keach file created. This program supports command-line operation: type splitmol -h for details. HH��ˆ������`����HH��ˆ��_eaa ���ff�l�����d���������������ee?�������� HH��ˆ������ c����HH��ˆ�������������e1�����HH��ˆ������c����HH��ˆ��bhdd���ff�l�����d���������������hh@�������� HH��ˆ������ f����HH��ˆ��)�����h2���b���a c ���aMolecule File Formats dY���a<Dock programs read and write in several coordinate formats. eh���m&ro'SYBYL MOL2 formatrp f���mrq'PDB formatrr g���mrs'PTR formatrt h���mru'SPH formatrv i ���irwSYBYL MOL2 format jժ���!{This format is used for general molecule input and output of &dock. Although previous versions of &dock 0ઢ���bsupported an extended PDB format to store molecule information, the current version now uses MOL2 ���has the primary molecule format. This format has the advantage of storing all the necessary information ���ifor atom features, position, and connectivity. It is also a standardized format that other modeling pro���Agrams can read. k !���aSpecification l5���a?Please refer to sybyl documentation for format specifications. mD���!hOf the many record types in a MOL2 file, &dock recognizes the following: MOLECULE, ATOM, BOND, 0O���fSUBSTRUCTURE and SET. In the MOLECULE record, &dock utilizes information about the molecule ���mname and number of atoms, bonds, substructures and sets. In the ATOM record &dock utilizes informa���qtion about the atom names, types, coordinates, and partial charges. In the BOND record, &dock utilizes ���pthe atom identifiers for the bond. In the SUBSTRUCTURE record, &dock records the fields, but does not ���iutilize them. The SET records are entirely optional. They are used only in special circumstances, like ���M<when rx)Ligand Flexibilityry is considered.. n ���aExample o���!jThis example file illustrates all the elements of the MOL2 file read and written by dock. It includes opŪ���MZtional SET records which are used by the rz)Ligand Flexibilityr{ routines. QpԪ��@ir| HH��ˆ������f����HH��ˆ��ekgg ���ff�l�����d���������������kkA�������� HH��ˆ������ i����HH��ˆ��>������k3����HH��ˆ������i����HH��ˆ��hnjj���ff�l�����d�������N?��������nnB�������� HH��ˆ������ l����HH��ˆ�������@n4��ADGJM�q ���ir}PDB format r���!jThis format should be used only for display purposes. Since it does not contain fields for atom types or 0���ppartial charges, vital information will be lost if dock output is routinely stored in this format. It is recom��� mended that all dock output be stored in either r~'SYBYL MOL2 formatr or r'PTR formatr. If you site does ���fnot have access to a method to view MOL2 format, just convert files to PDB when vewing is necessary. ���MSSee r'Molecule File Conversion' on page 54r for instructions. s z���irPTR format t ���aSpecification u���!ePTR (or pointer) format is a compact representation for molecules which does not actually contain co0���kordinates. Instead, it contains the transformations to the coordinates and "points" back to a source file ���A,where the untransformed coordinates reside. vת���!nAll information about a molecule is packed into one line. Each item of data is identified by a field name. 0⪟���hSome fields are required, like the molecule source information. Some are optional, like the coordinate ���ctransformation information. All others are considered comments and are ignored, like the molecule ���Aname and score information. wUT$UF��@irPTR Format Data Fields QxU?��@ir HH��ˆ�����NB�l����HH��ˆ��kqmm ���ff�l�����d�������NU��������qqC�������� HH��ˆ������ o����HH��ˆ��2�����Aq5�ADGJM��WyUTU0��@ir HH��ˆ�����NX�o����HH��ˆ��ntpp���ff�l�����d�������O��������ttD�������� HH��ˆ������ r����HH��ˆ��� ��� ��t6����z ���aExample {'��@irDatabase Entry |r��@irFlexible Docking Output }��@i$rChemical Screen Database Entry ~ P���aUsage d���mtCheck out the r'ptrentryr and r'ptrfieldr utilities to help manipulate PTR files. �s���!hThe <FILE> field can contain the relative path or absolute path of a filename. If you use the absolute 0~���qpath, then the ptr file can be used in any other directory. Otherwise, the ptr file is only useful in the idrec���A&tory in which it was originally made.  ���irSPH format Wɪ���maPlease refer to r'sphgen' on page 84r for a description of the file format. HH��ˆ�����O�r����HH��ˆ��qwss ���ff�l�����d�������O��������wwE�������� HH��ˆ������ u����HH��ˆ��x������w7�������a  ���aParameter Files  ^���a Introduction r���!jThe parameter files contain atom and bond data needed during &dock calculations. The definition 0}���i(*.defn) files contain atom and bond labeling data. The table (*.tbl) files contain additional data for ���A]chemical interactions and flexible bond torsion positions. They may be edited by the user.  ���irAtom definition rules ���!kThe definition files use a consistent atom labeling convention for which an atom in virtually any chemical 0Ǫ���henvironment can be identified. The specification of adjacent atoms is nested using the elements listed ���Mfin r'Table 7.r Some sample definitions are provided in r'Table 8.r  ᪣���a+Each element must be separated by a space.  ���!dIf more than one adjacent atom is specified, then ALL must be present (i.e. a boolean AND for rules ���Awithin a line).  ���!dIf a label can have multiple definition lines, then any ONE of them must be satisfied for inclusion ���A2(i.e. a boolean OR for rules on different lines).  UTAUH��@i#rrAtom definition elements Q U?��@irrExample definitions HH��ˆ�����O�u����HH��ˆ��tzvv���ff�l�����d�������O��������zzF�������� HH��ˆ������ x����HH��ˆ��� �������z8���� ���irvdw.defn ���aNThis file contains atom labels and definitions for van der Waals atom typing. ���!]The following data types are associated with each atom: VDW radius, VDW well-depth, flag for ���A&heavy atom, number of attached atoms. L���!`Some labels are used only for the united-atom model, some for only the all-atom model, and some W���A for either. f���a'A label may have multiple definitions. ���mvFor an explanation of the %definition field, see r'Atom definition rules' on page 104r. WUTUL��@i"rSample entries from vdw.defn HH��ˆ�����O�x����HH��ˆ��w}yy ���ff�l�����d�������O��������}}G�������� HH��ˆ������ {����HH��ˆ������ ��}9�������a  ���irchem.defn ���aAThis file contains labels and definitions for chemical labeling. J���a7Nothing in addition to a label is assigned to an atom. ���a,A label may have multiple definition lines. ���mvFor an explanation of the %definition field, see r'Atom definition rules' on page 104r. WUTUN��@irEntries from chem.defn HH��ˆ�����O�{����HH��ˆ��z�||���ff�l�����d�������S����������H�������� HH��ˆ������ ~����HH��ˆ��K����!���:�������a  ���irchem_match.tbl ���aiThis file contains the interaction matrix for which chemical labels can form an interaction in matching. J���mIThe labels must be identical to labels in r'chem.defnr.  ���aKThe %table flag indicates the beginning of the interaction table. !���a?Compatible labels are identified with a one, otherwise a zero. "���mvFor an explanation of the %definition field, see r'Atom definition rules' on page 104r. W#UTUM��@irExample of chem_match.tbl HH��ˆ�����S�~����HH��ˆ��} ���ff�l�����d�������S��������I�������� HH��ˆ������ ����HH��ˆ��V� ���"��;����$���a % ���irchem_score.tbl &���!hThis file contains the interaction matrix for how an chemical interaction score between chemical labels F���A is scaled. 'U���mIThe labels must be identical to labels in r'chem.defnr. (���aKThe %table flag indicates the beginning of the interaction table. )���a"Each element is a scaling factor. *���mvFor an explanation of the %definition field, see r'Atom definition rules' on page 104r. W+UTUL��@irExample of chem_score.tbl HH��ˆ�����S�����HH��ˆ������ff�l�����d�������V��������J�������� HH��ˆ������ ����HH��ˆ��V� ���#��<����,���a - ���irchem_screen.tbl .���!fThis file contains the interaction matrix for how to scale the contribution of each chemical key when F���A"computing the overall similarity. /U���mIThe labels must be identical to labels in r'chem.defnr. 0���aKThe %table flag indicates the beginning of the interaction table. 1���a"Each element is a scaling factor. 2���mvFor an explanation of the %definition field, see r'Atom definition rules' on page 104r. W3UTUL��@i rExample of chem_screen.tbl HH��ˆ�����V�����HH��ˆ��  ���ff�l�����d�������V�������� K�������� HH��ˆ������ ����HH��ˆ��� ���$�� =����4���` 5 ���hrflex.defn 6���`LThis file contains labels and definitions for flexible bond identification. 7J���lkThe %drive_id field corresponds to a torsion type in the r'flex_drive.tblr file. 8���`NThe %minimize field is a flag for whether the bond may be minimized. 9��� cTwo definition lines must be present. Each definition corresponds to an atom at either end of the s���@bond. :���lvFor an explanation of the %definition field, see r'Atom definition rules' on page 104r. W;UTUL��@h%rSelected entries from flex.defn HH��ˆ�����V�����HH��ˆ�� ���ff�l�����d�������X�������� L�������� HH��ˆ������ ����HH��ˆ��h����%�� >����<���a = ���irflex_drive.tbl >���-vThis file contains torsion positions assigned to each rotatable bond when the r*torsion_driver paramF���E eter is used in &dock. ?U���a?The %drive_id field corresponds to each torsion type. @���aPThe %positions field specifies the number of torsion angles to sample. A���aDThe %torsions field specifies the angles that are sampled. WBUTUM��@i+rSelected entries from flex_drive.defn HH��ˆ�����X� ����HH��ˆ��   ���ff�l�����d�������X��������M�������� HH��ˆ������ ����HH��ˆ���"���"����?����C���a D ���i rSources EY���acompiled by C.Corwin F y���i)r rAvailable Chemicals Directory G���aMDL Information Systems, Inc. H���a14600 Catalina Street I���aSan Leandro, CA 94577 J���aphone (510) 895-1313 K���afax (510) 352-2870 L ���aBrookhaven Protein Data Bank M���aProtein Data Bank N ���a#Chemistry Department, Building 555 O���aBrookhaven National Laboratory P���aUpton, NY 11973 Q���aphone (516) 282-3629 R���afax (516) 282-5751 S���ae-mail pdb@bnl.gov T���agopher://pdb.pdb.bnl.gov/11 U ���i.rrCambridge Crystallographic Database V���aFor industrial users: W���a+The Cambridge Crystallographic Data Centre X���a12 Union Road Y���a Cambridge Z���aCB2 1EZ [���aU.K. \���aphone +44 223 336408 ]���afax +44 223 336033 ^#���aFor US academic users: _3���aDr. William L. Duax `B���aMedical Foundation of Buffalo a���aResearch Laboratories b���a73 High Street c���aBuffalo, NY 14203-1196 Ad���aphone (716) 856-9600 HH��ˆ�����X� ����HH��ˆ�� ���ff�l�����d�������d%��������N�������� HH��ˆ������ ����HH��ˆ��a�!���!����@����e���`fax (716) 852-4846 f���`&e-mail WPPDS%mfb@edu.buffalo.cc.ubvms g���`Cambridge information h���`http://csdvx2.ccdc.cam.ac.uk iZ ]���`DelPhi jq���`Biosym Technologies k���`10065 Barnes Canyon Road l���`San Diego, CA 92121 m���`phone (619) 458-9990 n ���hrrGoodfords Zgrid oҪ���`Henrietta Elton p᪢���`Molecular Discovery Limited q���`West Way House, Elms Parade r���`Oxford OX2 9LL s���`ENGLAND t���`Phone +44-993-830385 u���`Fax +44-993-830966 vZ L���hrrisis w`���`MDL Information Systems, Inc. xo���`14600 Catalina Street y���`San Leandro, CA 94577 z���`phone (510) 895-1313 {���`fax (510) 352-2870 |Z ���h rrms }Ъ���lBsee r'Quantum Chemistry Program Exchange (QCPE)r ~ ���h/rQuantum Chemistry Program Exchange (QCPE) ���`Creative Arts Bldg. 181 ����`Indiana University ���`Bloomington, IN 47405 ���`phone (812) 855-5539 ���`fax (812) 855-4784 ���`e-mail qcpe@ucs.indiana.edu A���`:gopher://gopher.gdb.org/1ftp%3aqcpe6.chem.indiana.edu%40/ HH��ˆ�����d(�����HH��ˆ�� ���ff�l�����d�������d)��������O�������� HH��ˆ������ ����HH��ˆ����������A����Z ���hrrsybyl ���`Tripos Associates ���`1699 S. 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