title: Efficient evaluation of binding free energy using continuum electrostatics solvation.
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.
authors.affiliation: Department of Biochemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Danzhi
authors.initials: D
authors.lastname: Huang
authors.forename: Amedeo
authors.initials: A
authors.lastname: Caflisch
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases / Q000737:chemistry; D016333:HIV Protease / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000737:chemistry; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000737:chemistry; D011485:Protein Binding; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D017320:HIV Protease Inhibitors; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016333:HIV Protease