Hi,
> If the ligand L is not too small and several it's atoms are reasonably
> involved into binding interaction with receptor (so it is not the case of
> just
> one h-bond etc.) the ligand migt be reasonably divided into several
> disjoint atom groups G1,G2 ...Gn and the total decoupling free energy dG
> might be
> in my opinion calculated as dG = dG(G1) + dG(G2) + ... +dG(Gn) where
> dG(Gi) is the free energy contribution corresponding with decoupling of
> the
> atom group Gi while the rest of the ligand (L-Gi) remains fully
> interacting (and for each "i" plays the role of "natural" restraint).
What you would need to do is decouple each individual part i of the ligand
after the other, without switching on parts 1 to i-1 again, then the sum
of your transformations would be equal to the total dG(Bind). The last bit
would again need restraints though. The ligand gaining/losing
translational and rotational degrees of freedom is actually an important
part of the binding process that should be accounted for. Restraints are a
way to do this but your approach wouldn't do the same I believe.
Summarily, a ligand is more than the sum of its parts ;-)
Kind Regards,
Thomas
Dr. Thomas Steinbrecher
formerly at the
BioMaps Institute
Rutgers University
610 Taylor Rd.
Piscataway, NJ 08854
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Received on Tue Jan 03 2012 - 01:30:03 PST
