title: Fast and accurate determination of the relative binding affinities of small compounds to HIV-1 protease using non-equilibrium work.
abstract: 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 δW=7%. The nature of binding is discovered using the FPL approach. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Computational Chemistry Research Group, Ton Duc Thang University, Ho Chi Minh City, Vietnam; Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam. ngosontung@tdt.edu.vn.
authors.forename: Son Tung
authors.initials: ST
authors.lastname: Ngo
authors.affiliation: Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Leuven, B-3001, Belgium E-mail: minh.nguyen@kuleuven.be.
authors.forename: Huynh Minh
authors.initials: HM
authors.lastname: Hung
authors.affiliation: Computational Chemistry Research Group, Ton Duc Thang University, Ho Chi Minh City, Vietnam; Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam. minh.nguyen@kuleuven.be.|Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Leuven, B-3001, Belgium E-mail: minh.nguyen@kuleuven.be. minh.nguyen@kuleuven.be.
authors.forename: Minh Tho
authors.initials: MT
authors.lastname: Nguyen
mesh_terms: D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D056004:Molecular Dynamics Simulation; D013816:Thermodynamics
chemical_list: D017320:HIV Protease Inhibitors; D008024:Ligands; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1
keywords: HIV-1 protease; fast pulling ligand; nature of binding; non-equilibrium molecular dynamics; non-equilibrium work; relative binding affinity; rupture force; steered molecular dynamics