UNIT 8.4 Using DelPhi to Compute Electrostatic Potentials and Assess Their Contribution to Interactions

Abstract

There is a general agreement that electrostatic interactions play a significant role in the structure and function of biological molecules. However, obtaining quantitative estimation of the electrostatic energy requires computational models that capture the microscopic nature of the heterogeneous environment of macromolecules. This protocol offers elaboration on one of the common methods to calculate the electrostatic energetic contributions using continuum electrostatics. The method involves solving the Poisson-Boltzmann (PB) equation numerically and regarding the solute as having a homogenous dielectric constant. In order to apply this method, a three dimensional structure of the molecule derived from experimental data (crystallography, NMR) or modeling techniques is required. The protocol will focus on the DelPhi program (Accelrys Inc. San Diego), which is one of the most common programs used for the estimation of electrostatic free energy contribution. A simple procedure of assigning criteria and parameters (charge distribution, solvent and solute dielectric constants, iterations, grid resolution, etc) enables one to illustrate an electrostatic potential map and estimate the electrostatic free energy, although with limited accuracy.