Toward a universal model to calculate the solvation thermodynamics of druglike molecules: The importance of new experimental databases

David S. Palmer, Andrey I. Frolov, Ekaterina L. Ratkova, Maxim V. Fedorov

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

We demonstrate that a new free energy functional in the integral equation theory of molecular liquids gives accurate calculations of hydration thermodynamics for druglike molecules. The functional provides an improved description of excluded volume effects by incorporating two free coefficients. When the values of these coefficients are obtained from experimental data for simple organic molecules, the hydration free energies of an external test set of druglike molecules can be calculated with an accuracy of about 1 kcal/mol. The 3D RISM/UC method proposed here is easily implemented using existing computational software and allows in silico screening of the solvation thermodynamics of potential pharmaceutical molecules at significantly lower computational expense than explicit solvent simulations.

Original languageEnglish
Pages (from-to)1423-1429
Number of pages7
JournalMolecular Pharmaceutics
Volume8
Issue number4
DOIs
Publication statusPublished - 1 Aug 2011
Externally publishedYes

Keywords

  • bioavailability
  • drug discovery
  • hydration free energy
  • in silico
  • reference interaction site model
  • RISM
  • RISM/UC
  • screening
  • solubility
  • virtual

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