Journal
JOURNAL OF COMPUTATIONAL CHEMISTRY
Volume 37, Issue 31, Pages 2734-2742Publisher
WILEY
DOI: 10.1002/jcc.24502
Keywords
fast pulling ligand; non-equilibrium work; relative binding affinity; HIV-1 protease; rupture force; non-equilibrium molecular dynamics; steered molecular dynamics; nature of binding
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Funding
- Ton Duc Thang University (TDTU-DEMASTED)
- Vietnam Ministry of Education and Training
- KU Leuven Research Council
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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 delta < W >=7%. The nature of binding is discovered using the FPL approach. (C) 2016 Wiley Periodicals, Inc.
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