| Abstract
| - In order to study protein−protein nonbonded interactions, we present the development of a new reducedprotein model that represents each amino acid residue with one to three coarse grains, whose physical propertiesare derived in a consistent bottom-up procedure from the higher-resolution all-atom AMBER force field. Theresulting potential energy function is pairwise additive and includes distinct van-der-Waals and Coulombicterms. The van-der-Waals effective interactions are deduced from preliminary molecular dynamics simulationsof all possible amino acid homodimers. They are best represented by a soft 1/r6 repulsion and a Gaussianattraction, with parameters obeying Lorentz−Berthelot mixing rules. For the Coulombic interaction, coarsegrain charges are optimized for each separate protein in order to best represent the all-atom electrostaticpotential outside the protein core. This approach leaves the possibility of using any implicit solvent model todescribe solvation effects and electrostatic screening. The coarse-grained force field is tested carefully for asmall homodimeric complex, the magainin. It is shown to reproduce satisfactorily the specificity of the all-atom underlying potential, in particular within a PB/SA solvation model. The coarse-grained potential isapplied to the redocking prediction of three different protein−protein complexes: the magainin dimer, thebarnase−barstar, and the trypsin−BPTI complexes. It is shown to provide per se an efficient and discriminatingscoring energy function for the protein−protein docking problem that remains pertinent at both the globaland refinement stage.
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