Cargando…

Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation

Central in the variational implicit-solvent model (VISM) [Dzubiella, Swanson, and McCammon Phys. Rev. Lett.2006, 96, 087802 and J. Chem. Phys.2006, 124, 084905] of molecular solvation is a mean-field free-energy functional of all possible solute–solvent interfaces or dielectric boundaries. Such a fu...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Zhongming, Che, Jianwei, Cheng, Li-Tien, Dzubiella, Joachim, Li, Bo, McCammon, J. Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2011
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278970/
https://www.ncbi.nlm.nih.gov/pubmed/22346739
http://dx.doi.org/10.1021/ct200647j
_version_ 1782223631444606976
author Wang, Zhongming
Che, Jianwei
Cheng, Li-Tien
Dzubiella, Joachim
Li, Bo
McCammon, J. Andrew
author_facet Wang, Zhongming
Che, Jianwei
Cheng, Li-Tien
Dzubiella, Joachim
Li, Bo
McCammon, J. Andrew
author_sort Wang, Zhongming
collection PubMed
description Central in the variational implicit-solvent model (VISM) [Dzubiella, Swanson, and McCammon Phys. Rev. Lett.2006, 96, 087802 and J. Chem. Phys.2006, 124, 084905] of molecular solvation is a mean-field free-energy functional of all possible solute–solvent interfaces or dielectric boundaries. Such a functional can be minimized numerically by a level-set method to determine stable equilibrium conformations and solvation free energies. Applications to nonpolar systems have shown that the level-set VISM is efficient and leads to qualitatively and often quantitatively correct results. In particular, it is capable of capturing capillary evaporation in hydrophobic confinement and corresponding multiple equilibrium states as found in molecular dynamics (MD) simulations. In this work, we introduce into the VISM the Coulomb-field approximation of the electrostatic free energy. Such an approximation is a volume integral over an arbitrary shaped solvent region, requiring no solutions to any partial differential equations. With this approximation, we obtain the effective boundary force and use it as the “normal velocity” in the level-set relaxation. We test the new approach by calculating solvation free energies and potentials of mean force for small and large molecules, including the two-domain protein BphC. Our results reveal the importance of coupling polar and nonpolar interactions in the underlying molecular systems. In particular, dehydration near the domain interface of BphC subunits is found to be highly sensitive to local electrostatic potentials as seen in previous MD simulations. This is a first step toward capturing the complex protein dehydration process by an implicit-solvent approach.
format Online
Article
Text
id pubmed-3278970
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-32789702012-02-14 Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation Wang, Zhongming Che, Jianwei Cheng, Li-Tien Dzubiella, Joachim Li, Bo McCammon, J. Andrew J Chem Theory Comput Central in the variational implicit-solvent model (VISM) [Dzubiella, Swanson, and McCammon Phys. Rev. Lett.2006, 96, 087802 and J. Chem. Phys.2006, 124, 084905] of molecular solvation is a mean-field free-energy functional of all possible solute–solvent interfaces or dielectric boundaries. Such a functional can be minimized numerically by a level-set method to determine stable equilibrium conformations and solvation free energies. Applications to nonpolar systems have shown that the level-set VISM is efficient and leads to qualitatively and often quantitatively correct results. In particular, it is capable of capturing capillary evaporation in hydrophobic confinement and corresponding multiple equilibrium states as found in molecular dynamics (MD) simulations. In this work, we introduce into the VISM the Coulomb-field approximation of the electrostatic free energy. Such an approximation is a volume integral over an arbitrary shaped solvent region, requiring no solutions to any partial differential equations. With this approximation, we obtain the effective boundary force and use it as the “normal velocity” in the level-set relaxation. We test the new approach by calculating solvation free energies and potentials of mean force for small and large molecules, including the two-domain protein BphC. Our results reveal the importance of coupling polar and nonpolar interactions in the underlying molecular systems. In particular, dehydration near the domain interface of BphC subunits is found to be highly sensitive to local electrostatic potentials as seen in previous MD simulations. This is a first step toward capturing the complex protein dehydration process by an implicit-solvent approach. American Chemical Society 2011-12-19 2012-02-14 /pmc/articles/PMC3278970/ /pubmed/22346739 http://dx.doi.org/10.1021/ct200647j Text en Copyright © 2011 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Wang, Zhongming
Che, Jianwei
Cheng, Li-Tien
Dzubiella, Joachim
Li, Bo
McCammon, J. Andrew
Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation
title Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation
title_full Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation
title_fullStr Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation
title_full_unstemmed Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation
title_short Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation
title_sort level-set variational implicit-solvent modeling of biomolecules with the coulomb-field approximation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278970/
https://www.ncbi.nlm.nih.gov/pubmed/22346739
http://dx.doi.org/10.1021/ct200647j
work_keys_str_mv AT wangzhongming levelsetvariationalimplicitsolventmodelingofbiomoleculeswiththecoulombfieldapproximation
AT chejianwei levelsetvariationalimplicitsolventmodelingofbiomoleculeswiththecoulombfieldapproximation
AT chenglitien levelsetvariationalimplicitsolventmodelingofbiomoleculeswiththecoulombfieldapproximation
AT dzubiellajoachim levelsetvariationalimplicitsolventmodelingofbiomoleculeswiththecoulombfieldapproximation
AT libo levelsetvariationalimplicitsolventmodelingofbiomoleculeswiththecoulombfieldapproximation
AT mccammonjandrew levelsetvariationalimplicitsolventmodelingofbiomoleculeswiththecoulombfieldapproximation