Efficient evaluation of binding free energy using continuum electrostatics solvation

J Med Chem. 2004 Nov 4;47(23):5791-7. doi: 10.1021/jm049726m.

Abstract

The linear interaction energy (LIE) method is combined with energy minimization and finite-difference Poisson calculation of electrostatic solvation for the estimation of the absolute free energy of binding. A predictive accuracy of about 1.0 kcal/mol is obtained for 13 and 29 inhibitors of beta-secretase (BACE) and HIV-1 protease (HIV-1 PR), respectively. The multiplicative coefficients for the van der Waals and electrostatic terms are not transferable between BACE and HIV-1 PR although they are both aspartic proteases. The present approach is about 2 orders of magnitude faster than previous LIE methods and can be used for ranking large libraries of structurally diverse compounds docked by automatic computational tools.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Endopeptidases / chemistry
  • HIV Protease / chemistry
  • HIV Protease Inhibitors / chemistry
  • Models, Molecular
  • Protease Inhibitors / chemistry
  • Protein Binding*
  • Static Electricity
  • Thermodynamics*

Substances

  • HIV Protease Inhibitors
  • Protease Inhibitors
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • HIV Protease