A closed-form, analytical approximation for apparent surface charge and electric field of molecules

TL;DR

This paper introduces a simple, parameter-free closed-form approximation for calculating the apparent surface charge and electric field of molecules, significantly speeding up computations while maintaining high accuracy compared to numerical solutions.

Contribution

The authors derive a novel analytical formula for molecular electrostatic properties that offers computational efficiency and accuracy without fitting parameters, applicable to various molecular structures.

Findings

Achieves within 0.8 kcal/mol RMSD for hydration free energies of small molecules.

Provides electric field estimates in quantitative agreement with numerical solutions.

Maintains qualitative accuracy in complex structures like proteins and DNA.

Abstract

Closed-form, analytical approximations for electrostatic properties of molecules are of unique value, as these can provide computational speed, versatility, and physical insight. Here, we derive a simple, closed-form formula for the apparent surface charge (ASC), as well as for the electric field, generated by a molecular charge distribution in aqueous solution. The approximation, with no fitted parameters, is tested against numerical solutions of the Poisson equation, where it yields a significant speed-up. For neutral small molecules, the hydration free energies estimated from the closed-form ASC formula are within 0.8 kcal/mol RMSD from the numerical Poisson reference; the electric field at the surface is in quantitative agreement with the reference. Performance of the approximation is also tested on larger structures, including a protein, a DNA fragment, and a viral receptor-target complex. For all structures tested, a near quantitative agreement with the numerical Poisson reference is achieved, except in regions of high negative curvature, where the new approximation is still qualitatively correct. A unique efficiency feature of the proposed "source-based" closed-form approximation is that the ASC and electric field can be estimated individually at any point or surface patch, without the need to obtain the full global solution. An open source software implementation of the method is available: http://people.cs.vt.edu/~onufriev/CODES/aasc.zip