AMBER: Calculating solvation energies for MM-PBSA use

From: Thomas Steinbrecher <>
Date: Thu, 18 Sep 2003 14:43:37 +0200

Dear AMBER users,

I have some difficulties in using MM_PBSA to calculate the
binding free energy of MgATP bound to a protein binding
pocket. I use AMBER7 on Linux.

I have set up my system in xleap using the protein pdb-file
and the nucleotide parameters of Dr. Carlson from the AMBER
homepage. I equilibrated my system for 200ps and I have
analysed the following nanosecond of dynamics. Since the
protein is rather big, I have defined a shell of 25A around
my ligand and allowed only those residues to move using the
ibelly- command, similar to the calculations in the
biotin/streptavidin tutorial on the AMBER homepage.
Solvation was simulated by adding a Watercap of 25A radius
centered on the ligand and including these waters in the
moveable residues.

For the MM-PBSA calculations I wrote the coordinates of
amino acid residues within 20A of the ligand into snapshots
and ran the MM-PBSA-script over them. I know that by using
only a cutout of the protein I introduce an incorrect
protein-water-contact and a wrong dielectric constant 20A
away from my ligand. I assume that leads to the same error
in the complex and receptor snapshots, so the energy
difference should nevertheless be meaningful. I use delphi
V4 release1.1 to calculate the PB part.

The result, however, is a total binding energy of more than
+100 kcal/mole (Without entropy contribution, which would
make the value even more positive). Since the gas phase
energy is about -500 kcal/mole I presume something is wrong
with my calculation of the solvation energy.

Has someone experienced similar problems in MM-PBSA
calculations with Magnesium-nucleotides?
Could there be anything wrong with my setup?

Many thanks in advance for any helpful comments and sorry
(again) for the long post,

Kind regards,

Thomas Steinbrecher
Institut für physikalische Chemie
Albertstr. 23a
79108 Freiburg

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Received on Thu Sep 18 2003 - 13:53:00 PDT
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