Automated molecular simulation based binding affinity calculator for ligand-bound HIV-1 proteases

Journal of Chemical Information and Modeling
S Kashif SadiqPeter V Coveney

Abstract

The successful application of high throughput molecular simulations to determine biochemical properties would be of great importance to the biomedical community if such simulations could be turned around in a clinically relevant timescale. An important example is the determination of antiretroviral inhibitor efficacy against varying strains of HIV through calculation of drug-protein binding affinities. We describe the Binding Affinity Calculator (BAC), a tool for the automated calculation of HIV-1 protease-ligand binding affinities. The tool employs fully atomistic molecular simulations alongside the well established molecular mechanics Poisson-Boltzmann solvent accessible surface area (MMPBSA) free energy methodology to enable the calculation of the binding free energy of several ligand-protease complexes, including all nine FDA approved inhibitors of HIV-1 protease and seven of the natural substrates cleaved by the protease. This enables the efficacy of these inhibitors to be ranked across several mutant strains of the protease relative to the wildtype. BAC is a tool that utilizes the power provided by a computational grid to automate all of the stages required to compute free energies of binding: model preparation, equilibra...Continue Reading

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Citations

Sep 10, 2011·Journal of Chemical Information and Modeling·David W Wright, Peter V Coveney
Jan 14, 2011·Journal of the Royal Society, Interface·Shunzhou Wan, Peter V Coveney
Jun 3, 2009·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·P M A SlootM Bubak
May 20, 2009·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Radhika S SaksenaPeter V Coveney
Nov 7, 2015·Journal of Chemical Information and Modeling·Hannes H LoefflerChristopher Woods
Dec 21, 2016·Journal of Chemical Theory and Computation·Agastya P BhatiPeter V Coveney
Dec 23, 2016·Journal of Chemical Theory and Computation·Shunzhou WanPeter V Coveney
Jun 25, 2008·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·S Kashif SadiqPeter V Coveney
Dec 24, 2018·BMC Bioinformatics·Jumana DakkaShantenu Jha
Nov 13, 2020·Interface Focus·S J ZasadaP V Coveney
Mar 30, 2021·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Shunzhou WanPeter V Coveney
Apr 14, 2010·Journal of Chemical Information and Modeling·S Kashif SadiqPeter V Coveney
Mar 21, 2019·Journal of Chemical Theory and Computation·Andrew PottertonAndrea Townsend-Nicholson
Oct 5, 2012·Journal of Chemical Information and Modeling·Shunzhou Wan, Peter V Coveney
Apr 1, 2014·Journal of Chemical Theory and Computation·David W WrightPeter V Coveney
Jul 10, 2019·The Journal of Physical Chemistry. B·Zainab K SanusiHendrik G Kruger

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