Improved Treatment of 1-4 interactions in Force Fields for Molecular Dynamics Simulations

Abstract

Traditional force fields commonly use a combination of bonded torsional terms and empirically scaled non-bonded interactions to capture 1-4 energies and forces of atoms separated by three bonds in a molecule. While this approach can yield accurate torsional energy barriers, it often leads to inaccurate forces and erroneous geometries, and creates an interdependence between dihedral terms and non-bonded interactions, complicating parameterization and reducing transferability. In this paper, we demonstrate that 1-4 interactions can be accurately modeled using only bonded coupling terms, eliminating the need for arbitrarily scaled non-bonded interactions altogether. Furthermore by leveraging the automated parameterization capabilities of the Q-Force toolkit, we efficiently determine the necessary coupling terms without the need for manual adjustment. Our approach is first validated on a range of small molecule systems, encompassing both flexible and rigid structures, and shows a significant improvement in force field accuracy, obtaining sub-kcal/mol mean absolute error for every molecule tested. We further extend the bonded-only model for 1-4 interactions to Amber ff14sb, CHARMM36, and OPLS-AA force fields to reproduce ab initio gas and implicit solvent $\phi,\psi$ surfaces of alanine dipeptide.