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Fast and accurate determination of the relative binding affinities of small compounds to HIV‐1 protease using non‐equilibrium work
Author(s) -
Ngo Son Tung,
Hung Huynh Minh,
Nguyen Minh Tho
Publication year - 2016
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.24502
Subject(s) - affinities , binding affinities , hiv 1 protease , chemistry , work (physics) , binding energy , ligand (biochemistry) , human immunodeficiency virus (hiv) , molecular dynamics , computational chemistry , binding site , protease , thermodynamics , stereochemistry , receptor , physics , biology , biochemistry , atomic physics , enzyme , immunology
The fast pulling ligand (FPL) out of binding cavity using non‐equilibrium molecular dynamics (MD) simulations was demonstrated to be a rapid, accurate and low CPU demand method for the determination of the relative binding affinities of a large number of HIV‐1 protease (PR) inhibitors. In this approach, the ligand is pulled out of the binding cavity of the protein using external harmonic forces, and the work of pulling force corresponds to the relative binding affinity of HIV‐1 PR inhibitor. The correlation coefficient between the pulling work and the experimental binding free energy of R = − 0.95 shows that FPL results are in good agreement with experiment. It is thus easier to rank the binding affinities of HIV‐1 PR inhibitors, that have similar binding affinities because the mean error bar of pulling work amounts to δ W = 7 % . The nature of binding is discovered using the FPL approach. © 2016 Wiley Periodicals, Inc.