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

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• 作者：Ilja V. Khavrutskii ; Anders Wallqvist
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2010
• 出版时间：November 9, 2010
• 年：2010
• 卷：6
• 期：11
• 页码：3427-3441
• 全文大小：344K
• 年卷期：v.6,no.11(November 9, 2010)
• ISSN：1549-9626

文摘

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.