Prediction of SAMPL2 aqueous solvation free energies and tautomeric ratios using the SM8, SM8AD, and SMD solvation models

Abstract

We applied the solvation models SM8, SM8AD, and SMD in combination with the Minnesota M06-2X density functional to predict vacuum-water transfer free energies (Task 1) and tautomeric ratios in aqueous solution (Task 2) for the SAMPL2 test set. The bulk-electrostatic contribution to the free energy of solvation is treated as follows: SM8 employs the generalized Born model with the Coulomb field approximation, SM8AD employs the generalized Born approximation with asymmetric descreening, and SMD solves the nonhomogeneous Poisson equation. The non-bulk-electrostatic contribution arising from short-range interactions between the solute and solvent molecules in the first solvation shell is treated as a sum of terms that are products of geometry-dependent atomic surface tensions and solvent-accessible surface areas of the individual atoms of the solute. On average, three models tested in the present work perform similarly. In particular, we achieved mean unsigned errors of 1.3 (SM8), 2.0 (SM8AD), and 2.6 kcal/mol (SMD) for the aqueous free energies of 30 out of 31 compounds with known reference data involved in Task 1 and mean unsigned errors of 2.7 (SM8), 1.8 (SM8AD), and 2.4 kcal/mol (SMD) in the free energy differences (tautomeric ratios) for 21 tautomeric pairs in aqueous solution involved in Task 2.

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Acknowledgements

This work was supported by the Office of Naval Research under Grant N 00014-05-01-0538, the Army Research Office under Grant US ARMY RES LAB/W911NF09-1-0377, and the National Science Foundation (Grant CHE06-10183 and Grant CHE07-04974). Computational resources were provided by the Minnesota Supercomputing Institute.

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Correspondence to Christopher J. Cramer or Donald G. Truhlar.

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Ribeiro, R.F., Marenich, A.V., Cramer, C.J. et al. Prediction of SAMPL2 aqueous solvation free energies and tautomeric ratios using the SM8, SM8AD, and SMD solvation models. J Comput Aided Mol Des 24, 317–333 (2010). https://doi.org/10.1007/s10822-010-9333-9

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Keywords

  • Free energy
  • Generalized Born
  • Implicit solvation
  • Poisson equation
  • Solvation
  • Solvation modeling
  • Tautomerism