MidasPlus Noeshow Exercises

Noeshow is a MidasPlus extension program that assists in the visualization of NMR-related data. Noeshow can show distance constraint and torsion angle satisfaction on a model structure or on an ensemble of model structures. Noeshow can use constraints in the following formats:

* AMBER INTERFACE
* AMBER SANDER
* DIANA
* MARDIGRAS
* X-PLOR

Noeshow can also show all hydrogen hydrogen distances within a certain cutoff distance of specified hydrogens.

This document is a walkthrough of the basic functionality of noeshow; it is not a complete reference guide and omits mention of some less-commonly used aspects of noeshow. However, the noeshow manual page is appended to the end of this document and the manual page covers all features of noeshow in complete detail, though in a somewhat less readable style. If you will be using noeshow for "real" work, you should read the manual page after completing these exercises.

This exercise assumes basic familiarity with Midas from other exercises.*

Exercise 1 -- Converting and showing constraints

This exercise outlines the procedure for converting and displaying distance con straints. The steps outlined are:

* Distance constraint conversion
* Distance constraint display
* Saving constraint satisfaction data

Converting distance constraints

The "native" format for noeshow is AMBER INTERFACE format. Other con straint formats are converted to this format via conversion scripts. This exer cise shows the conversion (and use) of X-PLOR constraints. Converting other formats is very similar (typically just a different conversion script name). Con sult the noeshow manual page for the exact conversion procedure for your preferred constraint format.

FIrst, you need to make copies of the exercise data files. A script has been prepared to do this for you. To execute the script, type:

/usr/local/midas/demos/tutorial/noe/copy

This will create a subdirectory of your home directory named noe.ex with the exercise files in it. If you aren't already in your home directory, get there with:

cd

Then go to the noe.ex subdirectory with:

cd noe.ex

The first thing is to convert the X-PLOR distance constraints to noeshow's "native" format. The X-PLOR constraints are in the file noe.xplor. The conversion script also needs to have access to the PDB file of the model structure in order to check that it can match the constraints to atoms in the model. The PDB model structure is in model.pdb. Therefore, the command to convert the constraints and have them placed in a file named noe.cnst is:

xplor2amber model.pdb noe.xplor > noe.cnst

As mentioned above, the commands for converting other constraint formats are typically extremely similar. For example, the command to convert AMBER SANDER style constraints would be:*

sander2amber model.pdb noe.sander > noe.cnst

Consult the noeshow manual page for further details.

Starting Midas

Start Midas with the model structure displayed with:*

midas model.pdb*

Position the model structure however you prefer.

Showing violated constraints

To show the violated constraints on the model structure in Midas, type:

Command: noeshow noe.cnst

You will see some colored lines repre senting constraints between atoms in the structure. The yellow lines represent distances that are slightly too long to satisfy their constraints, whereas the cyan lines represent distances that are slightly too short. The model structure is fairly good. For a bad structure you would also see red lines (distance much too long) and dark blue lines (distance much too short).*

Violation criteria

What determines "slightly" too long versus "much" too long? Noeshow's "native" constraint format ( i.e. AMBER INTERFACE format) uses an "energy well" description of constraint satisfaction. There is a distance range where the constraint is completely satisfied (zero energy penalty). Outside of this range, there is a range where an energy penalty is increasingly heavily applied. Finally, outside this second range, a maximum energy penalty is applied. Distances in this last range are "much" too short/long whereas distances in the intermediate range are "slightly" too short/long.
X-PLOR format doesn't have an "energy well" description but instead has simple upper and lower bounds. To generate an energy well, the xplor2amber con version script uses the given bounds as the ends of the "zero energy penalty" and puts the "maximum energy penalty" area 0.5 angstoms beyond. This can be controlled with a command line option to xplor2amber, as described in the noeshow manual page.

Saving violations to a file

You may wish to save the constraint violation information to a file for later reference. If you run noeshow with the -f flag (followed by a file name), noeshow will store the violated constraints to that file, sorted by magnitude of violation. If the -n flag is also given, then the sign of the violation (negative is short) is also saved. So, to save constraint violation information from our current session to a file named viol.info, type the fol lowing command:

Command: noeshow -f viol.info noe.cnst

The -f flag works in addition to what noeshow already normally does. This means that a duplicate set of constraints is now showing. Close the duplicate set with:

Command: close obj 2

If you wish to see the saved violation information, you can page through the file with more:

more viol.info

Hitting the space bar will page through the file, and 'q' will quit.

Satisfied constraints*

It is sometimes desirable to see the satisfied constraints as well. First, remove the current constraints displayed with:*

Command: close obj 1

Then run noeshow with the -a option:

Command: noeshow -a noe.cnst

The numerous satisfied constraints are shown as green lines, with the violated constraints in their previous colors.
Note that the displayed constraints are in a "graphics object", i.e. a series of move/draw commands in various colors. The constraints cannot be referenced via an atom specification, e.g. the command:

Command: show #1 /color=cyan

will not show just the cyan constraints; instead it will have no effect. The constraints can only be acted on as a whole. For example, they can be undisplayed with:

Command: ~objdisplay 1

and redisplayed with:

Command: objdisplay 1

This completes Exercise 1; you can stop Midas.

Exercise 2 -- Showing torsions

Some NMR projects make use of torsion angle constraints and some don't. If you don't anticipate using torsion angle con straints in your work, you may want to skip this exercise and proceed with Exercise 3. Exercise 2 uses files gen erated during the preceeding exercise and therefore you must have completed Exercise 1 before doing this exercise.*
Noeshow can only use torsion information in one of two formats: AMBER for mat ( noeshow's "native" format) and X PLOR format (which must be converted, using a procedure very similar to that for distance contraints). This exercise uses X-PLOR format constraints, found in the file tors.xplor. The conversion pro cedure is similar to that for distance constraints:*

xplor2tors tors.xplor > noe.tors

Now start Midas with the model structure:*

midas model.pdb

To show the torsion constraints (along with the distance constraints), do:

Command: noeshow -A noe.cnst noe.tors

The -A flag causes all torsion constraints to be shown; otherwise only the violated torsions would have been depicted. The torsion constraints are drawn as color coded "cages" about the central bond of each torsion. You should probably scale up the image to get a good look at the various torsions.
The color scheme for the torsions re flects the degree of satisfaction. The exact meaning of each color depends on whether the torsions were generated by X-PLOR or AMBER:

                AMBER:               X-PLOR
          Energy penalty of:       Dihedral is...

Green        0.0              satisfied and not within 5 
                              degrees of extreme bounds

Yellow       <=1.0            satisfied but within 5
                              degrees of extreme bounds

Orange       <=4.0            violated by no more than 10 degrees

Red          >4.0             violated by more than 10 degrees

In this model structure no torsions are violated badly enough to be colored red.
Unlike distance constraints, noeshow does not yet support saving torsion violation information to a file.

You have completed Exercise 2. You may stop Midas now.

Exercise 3 -- Showing neighboring hydrogens

At times during NMR structure determination, it is useful to visually inspect which hydrogens are spatial neighbors of a particular hydrogen or hydrogens of interest. Though it is quite possible to carry out such an inspection in Midas Plus without noeshow, noeshow offers features that make such an inspection easier and more direct.
To demonstrate this use of noeshow, first go to the exercise directory (as per Exercise 1) and open the model struc ture:

midas model.pdb

Now it is necessary to indicate which hydrogen(s) are of main interest, i.e. which hydrogen(s) we should check for near neighbors. The MidasPlus mark command can be used to associate a secondary name with one or more atoms. Associating the name noemark1 with the main hydrogen(s) will indicate to noeshow that those are the hydrogens of main interest. First, we have to indicate to MidasPlus that we intend to use the name noemark1 with the command:

Command: makemark noemark1

Let us assume that the main atoms of interest are HG1 and HG2 of residue 27 (glutamic acid). Mark them with:

Command: mark noemark1 :27@HG=

and so we can identify them, color them with:

Command: color cyan /mark=noemark1

We should be all set to go, right? Unfortunately, no. Noeshow is written in a language called perl, which is quite powerful and thereby greatly reduced the time necessary for implementation. How ever, perl is not very fast at numerical calculations. Therefore it is best to indicate exactly which atoms distances need to be calculated to as well as from. We can do this by marking them with the name noemark2. Let's assume we're interested in other hydrogens within 5 angstroms of our HG protons. The commands to mark these other hydrogens are:

Command: makemark noemark2

Command: mark noemark2 /mark=noemark1 za<5.1

This later command marked (with the name noemarkz) all atoms within 5.1 angstroms of the atoms marked with the name noemark1. Now we are ready to run noeshow. To indicate that we are interested in monitoring H-H interactions of 5 angstroms or less we use the -h flag like so:

Command: noeshow -h 5

The resulting lines and distances look like a tangle unless we focus in on the region of interest with the window command:

Command: window /mark=noemark2

Also, it makes examination easier if the center of rotation is centered in the region of interest:

Command: cofr /mark=noemark2

After examinig the noeshow results, you have completed Exercise 3. You may stop Midas.