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

TL;DR

This paper refines Lennard-Jones parameters in force fields to improve the accuracy of molecular dynamics simulations involving amine-carboxylate and amine-phosphate interactions, enhancing realism without artifacts.

Contribution

It introduces a systematic refinement of force field parameters for better simulation of biomolecular assemblies involving amine interactions.

Findings

Enhanced agreement with experimental data

Maintained existing parameterization of bonded interactions

No adverse effect on solvation free energies

Abstract

Over the past decades, molecular dynamics (MD) simulations of biomolecules have become a mainstream biophysics technique. As the length and time scales amenable to the MD method increase, shortcomings of the empirical force fields---which have been developed and validated using relatively short simulations of small molecules---become apparent. One common artifact is aggregation of water-soluble biomolecules driven by artificially strong charge--charge interactions. Here, we report a systematic refinement of Lennard-Jones parameters (NBFIX) describing amine--carboxylate and amine--phosphate interactions, which brings MD simulations of basic peptide-mediated nucleic acids assemblies and lipid bilayer membranes in better agreement with experiment. As our refinement neither affects the existing parameterization of bonded interaction nor does it alter the solvation free energies, it improves realism of an MD simulation without introducing additional artifacts.