Improved Parameterization of Amine-Carboxyate and Amine-Phosphate Interactions for Molecular Dynamics Simulations Using the CHARMM and AMBER Force Fields

摘要

Over the past decades, molecular dynamics (MD) simulations of biomoleculeshave become a mainstream biophysics technique. As the length and time scalesamenable to the MD method increase, shortcomings of the empirical forcefields---which have been developed and validated using relatively shortsimulations of small molecules---become apparent. One common artifact isaggregation of water-soluble biomolecules driven by artificially strongcharge--charge interactions. Here, we report a systematic refinement ofLennard-Jones parameters (NBFIX) describing amine--carboxylate andamine--phosphate interactions, which brings MD simulations of basicpeptide-mediated nucleic acids assemblies and lipid bilayer membranes in betteragreement with experiment. As our refinement neither affects the existingparameterization of bonded interaction nor does it alter the solvation freeenergies, it improves realism of an MD simulation without introducingadditional artifacts.