Balancing All‐Atom Force Field for DNA Simulations Using Osmotic Pressure Data

Abstract

For classical molecular dynamics (MD) simulations of DNA molecules, several all‐atom force fields have been developed, including the very popular amber bsc1 force field. Despite marked improvement from the standard amber99 force field, this force field has a tendency to underestimate base‐pair hydrogen bonds and overestimate base stacking (BS). Previously, the weakened hydrogen bond with the bsc1 was improved by modulating a limited number of van der Waals sigma parameters. In this study, to resolve the remaining issue of overestimating BS, nonbonding interaction parameters relevant to the BS interaction were tuned, such that the experimental osmotic pressure coefficients of deoxy‐ribonucleoside solutions are closely reproduced. This newly modified force field is more balanced in terms of nonbonding interactions and can be applied to many challenging computational problems of DNA folding and breathing.