Accession Number:

ADA533552

Title:

Computing Relative Free Energies of Solvation Using Single Reference Thermodynamic Integration Augmented with Hamiltonian Replica Exchange

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH AND MATERIEL COMMAND FORT DETRICK MD

Report Date:

2010-10-21

Pagination or Media Count:

16.0

Abstract:

This paper introduces an efficient single-topology variant of Thermodynamic Integration TI for computing relative transformation free energies in a series of molecules with respect to a single reference state. The presented TI variant that we refer to as Single-Reference TI SR-TI combines well-established molecular simulation methodologies into a practical computational tool. Augmented with Hamiltonian Replica Exchange HREX, the SR-TI variant can deliver enhanced sampling in select degrees of freedom. The utility of the SR-TI variant is demonstrated in calculations of relative solvation free energies for a series of benzene derivatives with increasing complexity. Of note, the SR-TI variant with the HREX option provides converged results in a challenging case of an amide molecule with a high 13-15 kcalmol barrier for internal cistrans interconversion using simulation times of only 1 to 4 ns.

Subject Categories:

  • Medicine and Medical Research
  • Physical Chemistry
  • Atomic and Molecular Physics and Spectroscopy
  • Thermodynamics

Distribution Statement:

APPROVED FOR PUBLIC RELEASE