[gmx-users] Energy perturbation

[Anton Feenstra]

alexander yakovenko wrote:
> 
> Hi all,
> 
> Can you help me to solve the next problems.
[...snip...]
> How can I make quality minimization of docked complexes and compare
> they binding energy in most equal conditions take into account the
> difference of local water molecules energy.

If I understand you correctly, you have docked a number of different
ligands into a protein (the same one each time), and you want to 
ave this structure solvated and minimized? 

There are a few things that you need to consider: As you already 
mention, minimizing with the waters already added, gives lousy results 
for the protein and ligand as the water energy dominates. What you
could do, is first minimize protein and ligand in vacuum, then
add water and minimize again (that will optimize the protein-water
interface). You should be aware that genbox does not produce 'sensible'
orientations for the water it adds; it simply takes water from a
pre-equilibrated water box (spc216.gro) and throws away any water 
molecules that don't fit (overlap with protein, or stick out of your
box). So, this is not a nice procedure to add water into a binding
cavity. Unfortunately, I don't know right away of a better way to
do it. In any case, if after adding water, you first minimize with
position restraints on protein & ligand, you might get better 
results, since this will force the water to adapt and not the protein.

> Can I make it correctly with Simulating Annealing?

I don't see how that will help.

-- 
Groetjes,

Anton
 ________ ___________________________________________________________
|        | Anton Feenstra                                            |
| .      | Dept. of Pharmacochemistry - Vrije Universiteit Amsterdam |
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