Download 2. We need a molecule

Conformational Sampling Tutorial
1. Open the MOE program
2. We need a molecule:
> Click on "Builder" (right-hand panel, under "System"). The molecule builder panel opens.
> Click on "Groups", then, after the Groups panel opens, use the pull-down menu at its top
to select "Amino Acids (½).
> Click on "Asparagine (N)". A molecule is uploaded in the main MOE window.
> Close the Group & Minimize the Builder Panel. Look at the molecule. Is it an amino
acid? Why not?
> Select the offending aldehyde hydrogen (click on it), then restore your Builder panel and
click on "O" in order to convert it into oxygen. The obtained molecule is asparagine.
> Close the Builder Panel. Click, from the main menu, "Compute>Protonate 3D". The
Protonation panel opens. What do you think this is for? Do you understand the parameters
it includes? What do you expect to see after clicking on "OK"? Do you think that the choice
of a proteolytic species has any impact on the molecular energy calculation?
(Note: You really should try to figure out the answers to the asked questions BEFORE they
will be discussed. Cheating tip: If you place the mouse cursor over the elements, the MOE
interface will provide yellow pop-ups with some explanations... but I did not tell you that!)
3. Let's sample!
> From the main MOE menu, select "Compute>Conformations>Systematic search". Take
some time to analyze the opening panel and try to understand what the parameters mean.
> The listed torsions are making reference to the sequence number of the atoms in the
molecule – that is the absolute order in which they appear in the atom list. In order to find
out which are the carbons 1, 2 and 13, double click on any atom in the molecule. The atom
manager appears and provides the list of atoms.
> Since C 13 is a side chain atom, let's exclude the torsion involving it from sampling.
Highlight that torsion in the Systematic search panel, then hit "Remove".
> Default torsional increments are huge. Select first torsional axis, then press the "30"
button to allow for an increment of 30 instead of 120. Click again on the blackened axis, to
deselect (it won't deselect by itself). With the second axis, set the step at 10. What is the
problem with the first axis? Why should it be sampled with a larger step size?
> Select some other name for the resulting database of conformers and hit OK. The
database browser appears, featuring a series of conformers – unfortunately, void of any
information.
4. What do we have got? Analysis tools...
> Let us monitor the values of the driven torsions within the database panel. Therefore,
from the Database Viewer, pick "Compute>Conformation Geometry". Once the associated
panel is up, go to the MOE main window, press shift and pick, one after the other, the four
atoms forming the first driven torsion: carboxylate O, carboxylate C, alpha C and N.
Release the shift button and check whether, in the Conformation Geometry panel, the
"Dihedral Field" says "N-C-C-O". If so, click on "Measure". Notice that a column in the
Database viewer, containing the associated torsional angle value, has been added.
Repeat the process in order to add the second torsion "carboxylate C-alpha C-beta Camide C".
> Let us add the energy column to the database: from the Database Viewer, select
"Compute>Descriptors" and, from the upcoming list, select "E i3D Potential Energy".
Guess what "i3D" means? Try "indices 3D" – molecular descriptors requiring geometric
input?) You may enter "ene" in the Filter text area, to find the entry quickly. After selecting
the entry, hit OK. An energy column will promptly be added to the Database Viewer.
> In principle, you may now plot the energy surface E as a function of the two torsional
angles. Pick "Compute>Analysis>3D Plot" from the Database Viewer. Somehow, MOE
guessed our intention and suggests, by default, that the two torsions should be on X and
Y, with energy on Z. However, the plot is – graphically speaking – very poor. MOE is not a
plotting software – but one may export the columns from the Database Viewer and
visualize them with other plotting tools.
> Look at the 3D plot along the Z axis. The XY plane containing the driven variables, you
should see a plot of the systematic grid of the visited torsion values – with gaps
corresponding to conformers of too high energy, which were rejected from the database.
Remember the "van der Waals contact" filtering parameter in the "Systematic Search"
panel? Missing (X,Y) values correspond to physically impossible combinations of torsional
angles.
5. Let's get sophisticated: Enable on-fly geometry optimization!
> Redo the exercise, but now enable the "Energy Minimize resulting conformations"
button. Only non-redundant geometries (check the "RMS" parameter!) within "Cutoff"
kcal/mol with respect to the best optimum will be stored. Why do we obtain so few
conformers??