A coarse-grained protein-protein potential derived from an all-atom force field.
In order to study protein-protein nonbonded interactions, we present the development of a new reduced protein model that represents each amino acid residue with one to three coarse grains, whose physical properties are derived in a consistent bottom-up procedure from the higher-resolution all-atom AMBER force field. The resulting potential energy function is pairwise additive and includes distinct van-der-Waals and Coulombic terms. The van-der-Waals effective interactions are deduced from preliminary molecular dynamics simulations of all possible amino acid homodimers. They are best represented by a soft 1/r6 repulsion and a Gaussian attraction, with parameters obeying Lorentz-Berthelot mixing rules. For the Coulombic interaction, coarse grain charges are optimized for each separate protein in order to best represent the all-atom electrostatic potential outside the protein core. This approach leaves the possibility of using any implicit solvent model to describe solvation effects and electrostatic screening. The coarse-grained force field is tested carefully for a small 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 is applied to the redocking prediction of three different protein-protein complexes: the magainin dimer, the barnase-barstar, and the trypsin-BPTI complexes. It is shown to provide per se an efficient and discriminating scoring energy function for the protein-protein docking problem that remains pertinent at both the global and refinement stage.
Basdevant
Nathalie
N
Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement Université d'Evry-Val-d'Essonne Rue du Pere André Jarlan, 91025 Evry Cedex, France.
Borgis
Daniel
D
Ha-Duong
Tap
T
D000596:Amino Acids / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D055672:Static Electricity
D000596:Amino Acids; D011506:Proteins