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Journal of Computer-Aided Molecular Design

, Volume 24, Issue 4, pp 373–383 | Cite as

Rapid prediction of solvation free energy. 3. Application to the SAMPL2 challenge

  • Enrico O. PurisimaEmail author
  • Christopher R. Corbeil
  • Traian Sulea
Article

Abstract

The SAMPL2 hydration free energy blind prediction challenge consisted of a data set of 41 molecules divided into three subsets: explanatory, obscure and investigatory, where experimental hydration free energies were given for the explanatory, withheld for the obscure, and not known for the investigatory molecules. We employed two solvation models for this challenge, a linear interaction energy (LIE) model based on explicit-water molecular dynamics simulations, and the first-shell hydration (FiSH) continuum model previously calibrated to mimic LIE data. On the 23 compounds from the obscure (blind) dataset, the prospectively submitted LIE and FiSH models provided predictions highly correlated with experimental hydration free energy data, with mean-unsigned-errors of 1.69 and 1.71 kcal/mol, respectively. We investigated several parameters that may affect the performance of these models, namely, the solute flexibility for the LIE explicit-solvent model, the solute partial charging method, and the incorporation of the difference in intramolecular energy between gas and solution phases for both models. We extended this analysis to the various chemical classes that can be formed within the SAMPL2 dataset. Our results strengthen previous findings on the excellent accuracy and transferability of the LIE explicit-solvent approach to predict transfer free energies across a wide spectrum of functional classes. Further, the current results on the SAMPL2 test dataset provide additional support for the FiSH continuum model as a fast yet accurate alternative to the LIE explicit-solvent model. Overall, both the LIE explicit-solvent model and the FiSH continuum solvation model show considerable improvement on the SAMPL2 data set over our previous continuum electrostatics-dispersion solvation model used in the SAMPL1 blind challenge.

Keywords

Hydration Continuum solvation LIE Continuum van der Waals First hydration shell Prospective study 

Notes

Acknowledgments

This is National Research Council of Canada publication number 00000.

Supplementary material

10822_2010_9341_MOESM1_ESM.pdf (232 kb)
Supplementary material 1 (PDF 232 kb)

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Copyright information

© Her Majesty the Queen in Right of Canada 2010

Authors and Affiliations

  • Enrico O. Purisima
    • 1
    Email author
  • Christopher R. Corbeil
    • 1
  • Traian Sulea
    • 1
  1. 1.Biotechnology Research InstituteNational Research Council CanadaMontrealCanada

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