106 Deriving force field dihedral angle parameters that account for conformation-dependent solvation effects

Abstract

Dihedral angle parameters in force fields are often obtained with the help of quantum chemical calculations. These are usually performed in vacuum and it is assumed that the solvent model used in the molecular dynamics simulation (explicit or implicit) satisfactorily accounts for the major part of the solvation energy. However, there are certain nonspecific solvation effects that are not properly accounted for, in this approach. They relate to conformation-dependent solute polarization and solvation of conformation-dependent charge distribution. On an example of the glycosidic torsion, we show that the contribution resulting from these effects is substantial and provides important correction to the torsion potential. A parameterization procedure is suggested that incorporates the missing conformation-dependent solvation effects into the torsion parameters, based on the difference between the quantum mechanical self-consistent reaction field and Poisson–Boltzmann continuum solvation models. The suggested approach avoids double counting of solvation effects and provides parameters that may be used in combination with any of the widely used nonpolarizable discrete solvent models or with the continuum solvent models. Improvements are demonstrated for the latest AMBER RNA parameters. The suggested procedure may help to provide consistently better parameters than the conventional in vacuo parameterization approach.