CCL: Molegro

 Sent to CCL by: "Rene Thomsen" [rt!^!molegro.com]
 Hi all,
 For protein-ligand docking, we would consider a hexapeptide to be a
 big molecule (i.e. more than 15 flexible torsions).
 Since our docking procedure (which is build on genetic algorithms) is
 stochastic, different runs may find different energy minima. For
 simple problems (small ligands) a single run is usually enough. For
 more complex problems you should run several runs (20 or more), use
 the clustering options, and e.g return the five top-ranked poses.
 Ideally, the highest scoring pose represents the real binding mode of
 the molecule, but sometimes manual inspection can improve the pose
 ranking.
 A couple of suggestions:
 - Focus the search - make sure the search space you consider is not too large.
 - Consider constraining the search if you suspect a certain
 interaction to be present.
 - Check the preparation of the complex (protonation state, missing
 atoms, check for warning/errors in the docking wizard, ...).
 Regarding the cavities: our cavity detection algorithm is also
 stochastic, so cavity sizes may differ. However, if you get different
 cavities each time you run the cavity detection algorithm, there is
 probably no well-defined binding pocket - which will make it more
 difficult for the program to succeed.
 You are also welcome to mail us your structures, so that we can have a
 look at your data to see if anything seems wrong.
 Kind regards,
 Rene Thomsen
 ---
 Molegro
 Hoegh-Guldbergs Gade 10, Bldg. 1090
 DK-8000 Aarhus C
 Denmark
 www.molegro.com
 On 2/7/07, Richard Leo Wood rwoodphd(a)msn.com <owner-chemistry|ccl.net>
 wrote:
 
 Sent to CCL by: "Richard Leo Wood" [rwoodphd!A!msn.com]
 Hi all,
 My ligands are hexapeptides, so they are not really proteins, but I suppose
 could be classified as "small molecules".  They are known to inhibit
 the receptor I am trying to "dock" them to (actually I'm trying to
 estimate the binding energies to the receptor).
 I have a concern about the results that I am getting.  They don't seem to be
 reproducible.  That is, if I run the same docking calculation over and over
 again, I get different results.  I wonder why that is. I've noticed that the
 cavity sizes (for the largest cavity) vary from run to run, as well.
 I would think that if I used the same settings each time, I should get the same
 binding affinities, but I'm not.
 TIA,
 Richard