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

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 kcal/mol) barrier for internal cis/trans interconversion using simulation times of only 1 to 4 ns.

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Document Details

Document Type
Technical Report
Publication Date
Oct 21, 2010
Accession Number
ADA533552

Entities

People

  • Anders Wallqvist
  • Ilja V. Khavrutskii

Organizations

  • United States Army Medical Research and Development Command

Tags

Communities of Interest

  • Energy and Power Technologies

DTIC Thesaurus Topics

  • Application Software
  • Calorific Value
  • Chemistry
  • Computational Science
  • Energy
  • Free Energy
  • Geometry
  • High Performance Computing
  • Isomers
  • Molecular Dynamics
  • Molecular Mechanics Methods
  • Molecules
  • Sampling
  • Simulations
  • Small Molecules
  • Solvation
  • Topology

Readers

  • Distributed Systems and Data Platform Development
  • Quantum Chemistry