title: 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. Noteworthy, 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.
authors.affiliation: Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command, Fort Detrick, MD 21702.
authors.forename: Ilja V
authors.initials: IV
authors.lastname: Khavrutskii
authors.forename: Anders
authors.initials: A
authors.lastname: Wallqvist