Development of a Generalized Born Model Parametrization for Proteins and Nucleic Acids

Abstract

The generalized Born model proposed by Still and co-workers (Qui, D.; Shenkin, P. S.; Hollinger, F. P.; Still, W. C. J. Phys. Chem. A 1997, 101, 3005−3014) is parametrized specifically for proteins, peptides, and nucleic acids within the CHARMM all hydrogen and polar hydrogen force fields. A database of atomic electrostatic environments and molecular electrostatic solvation free energies comprising amino acid residues, nucleic acid bases, dipeptides, dinucleotides, proteins, and DNA strands is established, and numerical finite difference Poisson calculations are solved using atomic radii and charges from the corresponding force field parameters. These data provide the necessary input to parametrize generalized Born models for a particular force field. The performance of these models in reproducing overall molecular solvation trends is examined and found to be quite good. Furthermore, calculations of electrostatic solvation free energy differences suggest that conformational free energy changes are well reproduced. Finally, the utilization of this generalized Born model in molecular dynamics simulations (both with and without cutoffs) is shown to give excellent agreement with explicit solvent simulations of a small 56-residue protein in water.