QM/MM Simulations with the Gaussian Electrostatic Model: A Density-based Polarizable Potential

Abstract

The use of advanced polarizable potentials in quantum mechanical/molecular mechanical (QM/MM) simulations has been shown to improve the overall accuracy of the calculation. We have developed a density-based potential called the Gaussian electrostatic model (GEM), which has been shown to provide very accurate environments for QM wave functions in QM/MM. In this contribution we present a new implementation of QM/GEM that extends our implementation to include all components (Coulomb, exchange-repulsion, polarization, and dispersion) for the total intermolecular interaction energy in QM/MM calculations, except for the charge-transfer term. The accuracy of the method is tested using a subset of water dimers from the water dimer potential energy surface reported by Babin et al. ( J. Chem. Theory Comput. 2013 9, 5395-5403). Additionally, results of the new implementation are contrasted with results obtained with the classical AMOEBA potential. Our results indicate that GEM provides an accurate MM environment with average root-mean-square error <0.15 kcal/mol for every intermolecular interaction energy component compared with SAPT2+3/aug-cc-pVTZ reference calculations.

LICHEM 1.1: Recent Improvements and New Capabilities

“…The Gaussian Electrostatic Model (GEM) is a force field based on frozen molecular densities that can be used to represent the MM environment, as we have recently reported. 33 In our first proof-of-principle implementation, the total energy of the system in QM/GEM calculations is expressed by:…”

LICHEM 1.1: Recent Improvements and New Capabilities

“…GEM is a density-based polarizable force fields that uses Hermite Gaussians to reproduce the molecular electronic density of individual fragments, and includes separate terms for Coulomb, exchange-repulsion, polar-ization, charge-transfer, and dispersion. We have recently developed an initial implementation of QM/GEM in LICHEM that provides the ability to employ GEM for the MM environment 33 .…”

“…37,38 In the MM optimization, the environmental atoms are under restrain constants, which are gradually removed in each internal cycle, until all restraints are removed. 36 In this new update, LICHEM v1.1, we include four major capabilities: the long-range electrostatic corrections (QM/MM-LREC) approach, 22,23 the QM/GEM implementation, 33 the Quadratic string method (QSM) 35,39 for determining minimum-energy path, and the Restrained environment optimization. [36][37][38] .…”

“…The paper is organized as follows, in the next section (Methodology), we introduce a description for the new algorithms and approaches implemented in LICHEM. Given that the implementation details for LREC can be found elsewhere , 22,23,33 , and the QM/GEM implementation 33 is in the initial stages (the full implementation with pmemd.gem will be we reported in a forthcoming report), we will only provide a brief overview, and concentrate on the new implementation of the quadratic string method and the restrained environment optimization, and how they were incorporated into LICHEM QM/MM scheme.…”

Semi-Empirical Born–Oppenheimer Molecular Dynamics (SEBOMD) within the Amber Biomolecular Package

“…[30][31][32][33][34] Second, the way in which the QM and MM parts should interact is not straightforward. 16 Multiple technical suggestions to handle the way the MM charges influence the 3 QM part 26,[35][36][37] and specific van der Waals parameters to represent non-elestrostatic QM/MM interactions [38][39][40] have been suggested. Third, the choice of the atoms that are included in the QM region can greatly influence the chemical mechanisms that can be modeled.…”