Interactive Molecular Dynamics in Virtual Reality Is an Effective Tool for Flexible Substrate and Inhibitor Docking to the SARS-CoV-2 Main Protease.

Journal of Chemical Information and Modeling
Helen DeeksAdrian Mulholland


The main protease (Mpro) of the SARS-CoV-2 virus is one focus of drug development efforts for COVID-19. Here, we show that interactive molecular dynamics in virtual reality (iMD-VR) is a useful and effective tool for creating Mpro complexes. We make these tools and models freely available. iMD-VR provides an immersive environment in which users can interact with MD simulations and so build protein complexes in a physically rigorous and flexible way. Recently, we have demonstrated that iMD-VR is an effective method for interactive, flexible docking of small molecule drugs into their protein targets (Deeks et al. PLoS One 2020, 15, e0228461). Here, we apply this approach to both an Mpro inhibitor and an oligopeptide substrate, using experimentally determined crystal structures. For the oligopeptide, we test against a crystallographic structure of the original SARS Mpro. Docking with iMD-VR gives models in agreement with experimentally observed (crystal) structures. The docked structures are also tested in MD simulations and found to be stable. Different protocols for iMD-VR docking are explored, e.g., with and without restraints on protein backbone, and we provide recommendations for its use. We find that it is important for the ...Continue Reading


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Apr 14, 2006·Current Topics in Medicinal Chemistry·Po-Huang Liang
Jul 14, 2006·Antiviral Research·Bart L Haagmans, Albert D M E Osterhaus
Dec 6, 2006·Biochemistry·Vito GrazianoWalter F Mangel
Mar 1, 2007·Emerging Infectious Diseases·Lin-Fa WangBryan T Eaton
Oct 16, 2010·PloS One·Chi-Pang ChuckKam-Bo Wong
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