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D. Huang; A. Caflisch

Journal: J. Med. Chem.
Year: 2004
Volume: 47
Issue: 23
Pages: 5791-5797
DOI: 10.1021/jm049726m
Type of Publication: Journal Article

Amyloid Precursor Protein Secretases; Endopeptidases; HIV Protease; HIV Protease Inhibitors; Models, Molecular; Protease Inhibitors; Protein Binding; Static Electricity; Thermodynamics


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 β-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.