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Communication: Quantum polarized fluctuating charge model: A practical method to include ligand polarizability in biomolecular simulations

Source: J. Chem. Phys. 135, 231101 (2012); http://dx.doi.org/10.1063/1.3671638

Published 21 December 2011

KEYWORDS and PACS
Keywords
PACS
  • 87.15.Pc
    Electronic and electrical properties of biomolecules
  • 36.20.Ey
    Macromolecular conformation (statistics and dynamics)
  • 36.20.Kd
    Electronic structure and spectra of macromolecules
  • 87.19.Pp
    Biothermics and thermal processes in biology (higher organisms)
  • 87.15.ak
    Monte Carlo simulations in molecular biophysics
  • 87.15.B-
    Structure of biomolecules
  • YEAR: 2011
RELATED DATABASES
Web of Science

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PUBLICATION DATA
ISSN:
1553-9628 (online)
Publisher:
AIP is a member of CrossRef AIP
S. Roy Kimura, Ramkumar Rajamani, and David R. Langley
Department of Computer-Assisted Drug Design, Bristol-Myers Squibb R & D, 5 Research Parkway, Wallingford, Connecticut 06492, USA
We present a simple and practical method to include ligand electronic polarization in molecular dynamics (MD) simulation of biomolecular systems. The method involves periodically spawning quantum mechanical (QM) electrostatic potential (ESP) calculations on an extra set of computer processors using molecular coordinate snapshots from a running parallel MD simulation. The QM ESPs are evaluated for the small-molecule ligand in the presence of the electric field induced by the protein, solvent, and ion charges within the MD snapshot. Partial charges on ligand atom centers are fit through the multi-conformer restrained electrostatic potential (RESP) fit method on several successive ESPs. The RESP method was selected since it produces charges consistent with the AMBER/GAFF force-field used in the simulations. The updated charges are introduced back into the running simulation when the next snapshot is saved. The result is a simulation whose ligand partial charges continuously respond in real-time to the short-term mean electrostatic field of the evolving environment without incurring additional wall-clock time. We show that (1) by incorporating the cost of polarization back into the potential energy of the MD simulation, the algorithm conserves energy when run in the microcanonical ensemble and (2) the mean solvation free energies for 15 neutral amino acid side chains calculated with the quantum polarized fluctuating charge method and thermodynamic integration agree better with experiment relative to the Amber fixed charge force-field. ©2011 American Institute of Physics
History: Received 20 October 2011; accepted 2 December 2011; published 21 December 2011
Digital Object Identifier: http://dx.doi.org/10.1063/1.3671638

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