MM-PBSA results

From: Thomas Steinbrecher <>
Date: Fri, 21 Mar 2003 14:15:25 +0100

Dear AMBER users,

I have performed MM-PBSA calculations with AMBER7 on a
receptor with varying ligands. I simulated 1ns of dynamics
and extracted 100 snapshots for each complex.

The calculations were performed as in the MM-PBSA tutorial
distributed with AMBER, electrostatics were treated with
the Delphi program.

The calculations resulted in Binding Free Energies of -21
to -30 kcal/mole which are far to negative to be correct.
For a molecule that is know not to bind to the receptor -18
kcal/mole were obtained. Experimental data suggest Binding
Free Energies of about 7 kcal/mole.

My question is, can the lack of agreement between the
calculations and experimental data be attributed to a
structural change in the protein from a ligand bound to
unbound conformation that is to slow to be observed in my
Or are there other possible causes for such an offset
between the calculated and exerimental values?

>From several papers I consulted, I expected the MM-PBSA
method to produce Binding Free Energies that are in good
accordance with experimental data, so I wonder if I did
something wrong or if my system could be inappropriate for
treatment by the MM-PBSA method.

Thank you in advance for any suggestions/comments,

Thomas Steinbrecher
Received on Fri Mar 21 2003 - 14:53:02 PST
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