Efficient evaluation of binding free energy using continuum electrostatics solvation

TitleEfficient evaluation of binding free energy using continuum electrostatics solvation
Publication TypeJournal Article
Year of Publication2004
AuthorsHuang D., Caflisch A.
JournalJournal of Medicinal Chemistry
Date Published2004 Nov 4
Type of ArticleResearch Article
KeywordsAmyloid 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.



Alternate JournalJ. Med. Chem.
PubMed ID15509178
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