Efficient evaluation of binding free energy using continuum electrostatics solvation.

Danzhi Huang; Amedeo Caflisch

doi:10.1021/jm049726m

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Efficient evaluation of binding free energy using continuum electrostatics solvation.

Danzhi Huang·Amedeo Caflisch

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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.

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Amyloid Precursor Protein Secretases Endopeptidases HIV Protease HIV Protease Inhibitors Models, Molecular Protease Inhibitors Protein Binding Static Electricity Thermodynamics Journal Article Research Support, Non-U.S. Gov't

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Danzhi Huang, Amedeo Caflisch. 2004-11-04. Efficient evaluation of binding free energy using continuum electrostatics solvation.. https://doi.org/10.1021/jm049726m

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