Free energies of hydration for organic molecules from Monte Carlo simulations

Summary

Methods for the computation of free energies of solvation are reviewed, with emphasis on aqueous systems and discrete representation of the solvent molecules in Monte Carlo (MC) or molecular dynamics simulations. Precise results for small organic solutes can now be obtained routinely by MC/free energy perturbation calculations. The average error for computed free energies of hydration is 1.0 kcal/mol with the use of partial charges for the solutes from either OPLS unitedatom potential functions or from fitting to the electrostatic potential surface from 6-31G* ab initio calculations. A less rigorous, computationally more rapid method based on linear response theory is also found to be valuable and reduces the average error for the test set of 16 solutes to 0.6 kcal/mol.

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Jorgensen, W.L., Tirado-Rives, J. Free energies of hydration for organic molecules from Monte Carlo simulations. Perspectives in Drug Discovery and Design 3, 123–138 (1995). https://doi.org/10.1007/BF02174470

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Keywords

  • Molecular Dynamic
  • Molecular Dynamic Simulation
  • Monte Carlo
  • Monte Carlo Simulation
  • Free Energy