Adapting Poisson-Boltzmann to the self-consistent mean field theory: application to protein side-chain modeling

The Journal of Chemical Physics
P KoehlM Delarue

Abstract

We present an extension of the self-consistent mean field theory for protein side-chain modeling in which solvation effects are included based on the Poisson-Boltzmann (PB) theory. In this approach, the protein is represented with multiple copies of its side chains. Each copy is assigned a weight that is refined iteratively based on the mean field energy generated by the rest of the protein, until self-consistency is reached. At each cycle, the variational free energy of the multi-copy system is computed; this free energy includes the internal energy of the protein that accounts for vdW and electrostatics interactions and a solvation free energy term that is computed using the PB equation. The method converges in only a few cycles and takes only minutes of central processing unit time on a commodity personal computer. The predicted conformation of each residue is then set to be its copy with the highest weight after convergence. We have tested this method on a database of hundred highly refined NMR structures to circumvent the problems of crystal packing inherent to x-ray structures. The use of the PB-derived solvation free energy significantly improves prediction accuracy for surface side chains. For example, the prediction ac...Continue Reading

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Citations

Mar 8, 2016·Proteins·Thomas GaillardThomas Simonson
Jan 26, 2018·Journal of Chemical Information and Modeling·Jose ColbesCarlos A Brizuela

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Methods Mentioned

BETA
NMR

Software Mentioned

PB
SCWRL
MF
OPUS
AQUASOL
TREEPACK
CHARMM
SASA
SCMF
ROTA

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