title: General Model for Treating Short-Range Electrostatic Penetration in a Molecular Mechanics Force Field.
abstract: Classical molecular mechanics force fields typically model interatomic electrostatic interactions with point charges or multipole expansions, which can fail for atoms in close contact due to the lack of a description of penetration effects between their electron clouds. These short-range penetration effects can be significant and are essential for accurate modeling of intermolecular interactions. In this work we report parametrization of an empirical charge-charge function previously reported (Piquemal J.-P.; J. Phys. Chem. A2003, 107, 10353) to correct for the missing penetration term in standard molecular mechanics force fields. For this purpose, we have developed a database (S101×7) of 101 unique molecular dimers, each at 7 different intermolecular distances. Electrostatic, induction/polarization, repulsion, and dispersion energies, as well as the total interaction energy for each complex in the database are calculated using the SAPT2+ method (Parker T. M.; J. Chem. Phys.2014, 140, 094106). This empirical penetration model significantly improves agreement between point multipole and quantum mechanical electrostatic energies across the set of dimers and distances, while using only a limited set of parameters for each chemical element. Given the simplicity and effectiveness of the model, we expect the electrostatic penetration correction will become a standard component of future molecular mechanics force fields.
authors.affiliation: Department of Biomedical Engineering and Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States ; Department of Biomedical Engineering and Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Qiantao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Computational and Molecular Biophysics Program, Division of Biology & Biomedical Sciences, Washington University in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Rackers
authors.affiliation: Department of Biomedical Engineering and Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Chenfeng
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Biomedical Engineering and Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Rui
authors.initials: R
authors.lastname: Qi
authors.affiliation: Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Paris 06, UMR 7616 , Case Courrier 137, 4 Place Jussieu, F-75005 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Narth
authors.affiliation: Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Paris 06, UMR 7616 , Case Courrier 137, 4 Place Jussieu, F-75005 Paris, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Lagardere
authors.affiliation: Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Paris 06, UMR 7616 , Case Courrier 137, 4 Place Jussieu, F-75005 Paris, France.
authors.forename: Nohad
authors.initials: N
authors.lastname: Gresh
authors.affiliation: Department of Chemistry, Washington University in St. Louis , St. Louis, Missouri 63130, United States.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Ponder
authors.affiliation: Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Paris 06, UMR 7616 , Case Courrier 137, 4 Place Jussieu, F-75005 Paris, France.
authors.forename: Jean-Philip
authors.initials: JP
authors.lastname: Piquemal
authors.affiliation: Department of Biomedical Engineering and Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Ren