Hi,
> I calculate the average structure over the equilibrated part of the QM/MM
> MD, so I hope, I have a realistic ensemble.
Id still say that a single structure, average or not, is not a good
representation of an ensemble. Imagine a symmetric double well potential.
The average structure would sit on top of the energy barrier and does not
capture either of the relevant low energy conformations. Add the rugged
landscape of a protein and minimization may not get you very far from the
bad average structure. Why not at least minimize 1000 complex structures
from MD and average the energy if you cant use MMPBSA?
> I try to calculate MM-GBSA and PBSA, but I got positive values for PBtot
> (for example 60.41 kcal and GBtot 2.02 kcal/mol) When I search for the
Are you sure that the Zn ion is the reason for the problematic results?
Adjusting the Zn radius or distributing some of the charge to its ligands
may help, but i agree that this doesnt sound very hopeful. However, the
approach you suggest amounts to just taking the E(GAS) from MMPBSA and
hoping it will tell you something about ligand binding, which it may well
not.
> the failure. Can I use the QM/MM-MD for the MM-GBSA calculations?
AFAIK not without tweaking the scripts.
> I restraint the md simulation relatively restrictive, by reason of time,
> could there be the failure?
Artificial restraints would tend towards not giving you a good structural
ensemble, but I doubt the effect is very big if your starting structure is
reasonable.
> Yes I know, that the Khandelwal et. al (2005)paper is due to methods not
> the best, but my boss like QM/MM calculation and Khandelwal got an rē of
> 0.9 with this approach. So we try to go this way, but with the Amber
> forcefield.
On the danger of sounding snarky, 'not the best methods' would tend to
give 'not the best results', prior publications notwithstanding ;-)
Kind Regards,
Thomas
Fruehlingshaft? Hier eher nicht...
Dr. Thomas Steinbrecher
formerly at the
BioMaps Institute
Rutgers University
610 Taylor Rd.
Piscataway, NJ 08854
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Received on Thu Mar 10 2011 - 04:00:06 PST
