This demo displays the HIV-1 protease.
The structure was solved by the members of Crystallography Laboratory, NCI-FCRF,
using synthetic protein supplied by CalTech.
To run the demo:
1) Open the hivmatch session: midas -f hivmatch (on a DEC Alpha, substitute "-fullscreen" for "-f")
2) To run the demo, type "1", and return.
This will run the first part of the demo.
command: 1 What will happen:
a) The hiv protease dissapears off the screen, and will come rolling in
onscreen.
All these commands are in a script. Script files are important tools for
creating videos.
b) The protease will get to the center of the screen and rotate around.
It is a dimer, where one subunit is yellow and the other cyan. The active
site aspartates are in red.
c) The active site is the "hole" bettween the dimer subunits. Only the
backbone atoms of the protein are being displayed. We will see the rest
later.
d) The AIDS virus causes the infected cell to make a long strand of protein,
that the HIV-1 protease (shown in this demo) chops up into the appropriate
viral building blocks. The active site is where the protease grabs on to
this protein strand, in order to cut it into pieces. A piece of inhibitor
will actually come into the active site. This inhibitor was crystallized
along with the protease, and its structure determined.
e) A ribbon structure will appear, showing the sheets and helices, with
the inhibitor in place.
f) A Van Der Waals surface will appear on the inhibitor, and it will rotate.
g) Binding to an inhibitor causes the shape of the protein to change. The
flaps on top come down to help hold the inhibitor into the active site (looks
like pac-man). The molecule will blink back and forth between open and closed
conformation in wireframe model. Then a program called tst will be run that
blinks back and forth between fully rendered ribbon images of the open and
closed conformations of the molecule, with captions.
h) Finally, all the atoms will be shown, not just the backbone, and a Conic
image will scroll up the screen. Of course, each sphere represents an atom,
and we can now see that the inhibitor fills the active site, and is packed
in fairly tightly.
3) If your workstation has stereo viewing hardware, you can see the protein
in stereo, with the "watch" option on, and the inhibitor selected, simulating
drug docking in stereo, by typing "2". Alternatively, If you just want it
to be rotating in stereo, type "3". If you don't want it to roll, do an
~roll. Have fun!