A Self-Consistent Space-Domain Decomposition Method for QM/MM Computations of Protein Electrostatic Potentials

Abstract

This paper introduces a self-consistent computational protocol for modeling protein electrostatic potentials according to static point-charge model distributions. The protocol involves a simple space-domain decomposition scheme where individual molecular domains are modeled as Quantum-Mechanical (QM) layers embedded in the otherwise classical Molecular-Mechanics (MM) protein environment. ElectroStatic-Potential (ESP) atomic charges of the constituent molecular domains are computed, to account for mutual polarization effects, and iterated until obtaining a self-consistent point-charge model of the protein electrostatic potential. The novel protocol achieves quantitative agreement with full QM calculations in the description of electrostatic potentials of small polypeptides where polarization effects are significant, showing a remarkable improvement relative to the corresponding electrostatic potentials obtained with popular MM force fields. The capabilities of the method are demonstrated in several applications, including calculations of the electrostatic potential in the potassium channel protein and the description of protein-protein electrostatic interactions.

Computational insights into the O2-evolving complex of photosystem II

“…Thus, the electrostatic interactions computed at the MM level in E MM,X and E MM,full cancel and the resulting DFT QM/MM evaluation of the total energy involves a quantum mechanical description of the polarization of the reduced system, due to the electrostatic influence of the surrounding protein environment. Polarization of the protein active site induced by the distribution of charge in the QM layer has been introduced by correcting the atomic charges of amino-acid residues in close contact with the QM layer, according to the self-consistent polarization protocol MoD-QM/ MM (Gascon et al 2006;Sproviero et al 2006b;Sproviero et al 2007c;Sproviero et al 2007e).…”

Computational Studies of the Primary Phototransduction Event in Visual Rhodopsin

“…The analysis of electrostatic potential (ESP) atomic charges 27 indicates that the reorientation of the two polarized bonds N-H(+) and C15-H, during the isomerization process, accounts for the displacement of the net positive charge at the linkage relative to the negatively charged counterion Glu-113, even when the linkage itself remains almost undisplaced.…”

LICHEM: A QM/MM program for simulations with multipolar and polarizable force fields

“…A smaller number of software packages allow atomic multipoles, polarizabilties, and/or diffuse charges to be added to the MM potential [21, 22, 44, 65–68]. Often, introducing these electrostatic models requires modifying the self–consistent field (SCF) routines in the QM software packages.…”