[gmx-users] Docking validation

[Mostafa Javaheri]

Dear Justin
I docked a ligand to a hetrodimer protein, I know the approximate
position of the ligand but I don't know whether or not the docked
ligand is relaxed in the binding site or is it taken the proper
orientation? I run the ligand-protein complex for 5ns MD by using
charmm force field and applied position restraint and constraint
forall bonds (ligand parameters obtained from swissparam server).
Should I apply restraint and constraint? Or I have to remove them for
better flexibility if its yes how should I remove them? And will the
simulation be correct if I remove them? Could I mark some residue of
binding site to force them to interact with the ligand? How?
To understand whether simulation could or not predict the correct
position of a ligand, I docked another ligand to its binding site
which their crystallographic structure had been provided before, I
used the worst docking pose for performing the same MDS, at last I
compared the positions of two ligands (crystallographic and
simulated), simulation hardly changed the position of the ligand after
5ns although its position energetically was wrong (based on docking
and crystallographic pdb file). If MDS continue for several µs will
the ligand find the correct position and orientation?  Given that I
couldn't meet such a MDS how can I speed up this simulation? Will it
be useful to mark some residues for interaction or put the ligand near
the binding site by dragging or do a flexible docking?
Sincerely
M.Javaheri