A Closed-Form, Analytical Approximation for Apparent Surface Charge and Electric Field of Molecules

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 have derived 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, was tested against numerical solutions of the Poisson equation, where it has produced 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 was 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 was 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: https://people.cs.vt.edu/~onufriev/CODES/aasc.zip.