An optimized charge penetration model for use with the AMOEBA force field

Abstract

The principal challenge of using classical physics to model biomolecular interactions is capturing the nature of short-range interactions that drive biological processes from nucleic acid base stacking to protein-ligand binding. In particular most classical force fields suffer from an error in their electrostatic models that arises from an ability to account for the overlap between charge distributions occurring when molecules get close to each other, known as charge penetration. In this work we present a simple, physically motivated model for including charge penetration in the AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications) force field. With a function derived from the charge distribution of a hydrogen-like atom and a limited number of parameters, our charge penetration model dramatically improves the description of electrostatics at short range. On a database of 101 biomolecular dimers, the charge penetration model brings the error in the electrostatic interaction energy relative to the ab initio SAPT electrostatic interaction energy from 13.4 kcal/mol to 1.3 kcal/mol. The model is shown not only to be robust and transferable for the AMOEBA model, but also physically meaningful as it universally improves the description of the electrostatic potential around a given molecule.

Assessing many-body contributions to intermolecular interactions of the AMOEBA force field using energy decomposition analysis of electronic structure calculations

“…As we have mentioned, permanent electrostatic interaction described by distributed point multipoles starts to break down in the overlapping regime due to the charge penetration effect. Two models previously explored by Rackers et al 80 that are able to incorporate this effect in AMOEBA are considered in this work: one by Gordon and co-workers. 1, 3 (originally used in the EFP model) and…”

“…This is mostly for the sake of simplicity, as the accuracy of the strictly 2-body permanent electrostatics is not the focus of our present paper. The equations required for extending these models to higher-order multipoles can be derived by appropriately differentiating the one-and two-site damping functions, which were reported by Rackers et al 80 The polarization effect in AMOEBA is modeled by induced dipoles, ! !…”

Non-covalent interactions across organic and biological subsets of chemical space: Physics-based potentials parametrized from machine learning

“…Rackers et al proposed an interesting framework that assumes a simplified functional form for the damping term and factors out of the entire interaction matrix T ij ξ . 44 We have not attempted to express Eq. (9) for the interaction matrix T ij ξ of all multipoles.…”

Raising the Performance of the Tinker-HP Molecular Modeling Package [Article v1.0]

“…Future work will focus on the algorithmic boosting of our initial implementation of classical non-polarizable force fields. In addition, the next iteration of the paper will propose more detailed benchmarks for new polarizable approaches, including SIBFA [35,36] and ongoing modifications of AMOEBA such as AMOEBA+ [37] and HIPPO [38,39].…”