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Applicability of a thermodynamic cycle approach for a force field parametrization targeting non-aqueous solvation free energies

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Abstract

Accurate solvation free energy ΔGsolv predictions require well parametrized force fields. In order to refit Lennard-Jones (LJ) parameters for improved ΔGsolv predictions for a variety of compound classes and chemical environments, a large number of ΔGsolv calculations is required. As the calculation of ΔGsolv is computational expensive, there is need for efficient but precise calculation methods. In this work, we focus on the computation of non-aqueous solvation free energies. We compare ΔGsolv results from highly precise reference simulations for transferring a solute from the vacuum into a condensed phase and results obtained from a thermodynamic cycle implementation. As test systems, we alter LJ parameters ε and σ of widely used GAFF atom types ca, cl, n1, oh and os in various solute/solvent combinations. We examine the degree of configurational space overlap and find an impact by hydrogen bonds and the solvent accessible surface area. We conclude that the application of a thermodynamic cycle for the parametrization of force fields targeting ΔGsolv is useful if the adaptation of LJ parameters is limited to atom types in the solute or if only ε is changed.

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Acknowledgements

Andreas Mecklenfeld acknowledges funding by a Georg-Christoph-Lichtenberg Fellowship by the Federal State of Lower Saxony, Germany. The authors declare no competing financial interest. Molecular dynamics simulations were performed with resources provided by the North-German Supercomputing Alliance (HLRN). We greatly appreciate the support.

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  1. Institut für Thermodynamik, Technische Universität Braunschweig, Hans-Sommer Strasse 5, 38106, Braunschweig, Germany

    Andreas Mecklenfeld & Gabriele Raabe

  2. Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Franz-Liszt-Strasse 35a, 38106, Braunschweig, Germany

    Andreas Mecklenfeld

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Mecklenfeld, A., Raabe, G. Applicability of a thermodynamic cycle approach for a force field parametrization targeting non-aqueous solvation free energies. J Comput Aided Mol Des 34, 71–82 (2020). https://doi.org/10.1007/s10822-019-00261-5

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