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The SAMPL4 hydration challenge: evaluation of partial charge sets with explicit-water molecular dynamics simulations

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Abstract

We used blind predictions of the 47 hydration free energies in the SAMPL4 challenge to test multiple partial charge models in the context of explicit solvent free energy simulations with the general AMBER force field. One of the partial charge models, IPolQ-Mod, is a fast continuum solvent-based implementation of the IPolQ approach. The AM1-BCC, restrained electrostatic potential (RESP) and IpolQ-Mod approaches all perform reasonably well (R2 > 0.8), while VCharge, though faster, gives less accurate results (R2 of 0.5). The AM1-BCC results are more accurate than those of RESP for tertiary amines and nitrates, but the overall difference in accuracy between these methods is not statistically significant. Interestingly, the IPolQ-Mod method is found to yield partial charges in very close agreement with RESP. This observation suggests that the success of RESP may be attributed to its fortuitously approximating the arguably more rigorous IPolQ approach.

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Acknowledgments

The authors thank David Mobley, Karisa Wymer, and Christopher Fennell, for providing their data for additional analysis in this paper. This study was made possible in part by grant GM61300 from the NIGMS. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. MKG is a founder of and has an equity interest in VeraChem LLC. Although grant GM61300 has been identified for conflict of interest management, the research findings included in this particular publication may not necessarily relate to the interests of VeraChem LLC. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.

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  1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, Room# 3224, La Jolla, CA, 92093-0736, USA

    Hari S. Muddana, Neil V. Sapra, Andrew T. Fenley & Michael K. Gilson

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  1. Hari S. Muddana
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  2. Neil V. Sapra
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Correspondence to Michael K. Gilson.

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Muddana, H.S., Sapra, N.V., Fenley, A.T. et al. The SAMPL4 hydration challenge: evaluation of partial charge sets with explicit-water molecular dynamics simulations. J Comput Aided Mol Des 28, 277–287 (2014). https://doi.org/10.1007/s10822-014-9714-6

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