AMBER Archive (2002)

Subject: MM-PBSA philosophy

From: Michal Otyepka (otyepka_at_aix.upol.cz)
Date: Wed Mar 20 2002 - 06:34:24 CST

Dear AMBER users,

an MM-PBSA analysis was done using only the trajectory for a complex. We
have computed dG energy of complex, dG ligand (from the same trajectory,
the other atoms were ignored) and dG protein. We have tried to publish our
results but refree wrote us :
"One cannot ignore intarmolecular strain energy and cannot derive the MM
energy of the complex, the ligand and the protein from a single snapshot.
Binding energy is defined as follows:
<Emm(bind)>=<Emm(complex)>-<Emm(free ligand)>-<Emm(free receptor)>
One can justify to some extent replacing the average energies by minimum
energies, but the minimum energy of the ligand in isolation (vacuum or
water) is NOT the same as the energy of that ligand while bound in the
complex, the difference being the intramolecular strain energy. The same
applies to the receptor. The authors shoul justify doing that (using only
trajectory for complex), although I am afraid I cannot imagine any
justification. To my mind, one cannot avoid carrying out independent
simulation of the ligand, the protein and the complex."

Could anybody tell me what is the MM-PBSA philosophy - to use 3
trajectories (complex, ligand, protein) or use only 1 trajectory for
complex? I think the original papers use only 1 trajectory for ddG
evaluation.

Thank you very much in advance for your help.

                                        Michal Otyepka

      
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