Computing Relative Free Energies of Solvation using Single Reference Thermodynamic Integration Augmented with Hamiltonian Replica Exchange.
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2010-12-14
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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