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Predicting skin permeability using the 3D-RISM-KH theory based solvation energy descriptors for a diverse class of compounds

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Abstract

The state-of-the-art molecular solvation theory is used to predict skin permeability of a large set of compounds with available experimental skin permeability coefficient (logKP). Encouraging results are obtained pointing to applicability of a novel quantitative structure activity model that uses statistical physics based 3D-RISM-KH theory for solvation free energy calculations as a primary descriptor for the prediction of logKP with relative mean square error of 0.77 units.

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Notes

  1. A summary of most prominent models developed for logKP prediction is presented in Table S1 in the ESM.

  2. This is a modified SPC point charge model of water with additional LJ parameters for the hydrogens (σH = 1.1 Å, εH = 0.046 kcal/mol) to avoid convergence issues and getting correct thermodynamics in 1D-RISM-KH theory.

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Acknowledgements

This work was financially supported by the NSERC Discovery Grant (RES0029477), and Alberta Prion Research Institute Explorations VII Research Grant (RES0039402). Generous computing time provided by WestGrid (www.westgrid.ca) and Compute Canada/Calcul Canada (www.computecanada.ca) is acknowledged.

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Authors and Affiliations

  1. Department of Mechanical Engineering, 10-203 Donadeo Innovation Centre for Engineering, University of Alberta, 9211-116 Street NW, Edmonton, AB, T6G 1H9, Canada

    Vijaya Kumar Hinge, Dipankar Roy & Andriy Kovalenko

  2. Nanotechnology Research Centre, 11421 Saskatchewan Drive, Edmonton, AB, T6G 2M9, Canada

    Vijaya Kumar Hinge, Dipankar Roy & Andriy Kovalenko

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  1. Vijaya Kumar Hinge
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  2. Dipankar Roy
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  3. Andriy Kovalenko
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Correspondence to Andriy Kovalenko.

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Hinge, V.K., Roy, D. & Kovalenko, A. Predicting skin permeability using the 3D-RISM-KH theory based solvation energy descriptors for a diverse class of compounds. J Comput Aided Mol Des 33, 605–611 (2019). https://doi.org/10.1007/s10822-019-00205-z

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