Volume 42 Issue 10
Oct.  2021
Turn off MathJax
Article Contents
WU Xuwei, LI Xingyu, LI Hua, LI Zhenhai, CHEN Wei, LI Dechang. Molecular Simulation Study on the Interaction Between SARS-CoV-2 Main Protease and the Antiviral Inhibitors[J]. Applied Mathematics and Mechanics, 2021, 42(10): 1081-1090. doi: 10.21656/1000-0887.420280
Citation: WU Xuwei, LI Xingyu, LI Hua, LI Zhenhai, CHEN Wei, LI Dechang. Molecular Simulation Study on the Interaction Between SARS-CoV-2 Main Protease and the Antiviral Inhibitors[J]. Applied Mathematics and Mechanics, 2021, 42(10): 1081-1090. doi: 10.21656/1000-0887.420280

Molecular Simulation Study on the Interaction Between SARS-CoV-2 Main Protease and the Antiviral Inhibitors

doi: 10.21656/1000-0887.420280
  • Received Date: 2021-09-13
  • Rev Recd Date: 2021-09-27
  • In this study, we studied the interactions between the inhibitors and the main protease (Mpro) of SARS-CoV-2, to understand how the inhibitors influence the dynamics of Mpro of SARS-CoV-2. Firstly, we applied molecular docking to obtain the binding complex of the inhibitors and the main protease, and the binding affinities. The classical molecular dynamics simulations showed that all of the tested inhibitors cannot inhibit the dynamics of Mpro’s active pocket. The replica-exchange molecular dynamics simulations showed that the inhibitors influence the shape of the active pocket of Mpro. With the formation of hydrogen bonds between the inhibitor and different sites of the active pocket, the inhibitors affect the length and width of the pocket. Our study indicated that the drug design of Mpro should fully consider the importance of the hydrogen network between the potential inhibitor and the active pocket.
  • loading
  • [2]HUANG C L, WANG Y M, LI X W, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J].The Lancet,2020,395(10223): 497-506.
    ZHU N, ZHANG D Y, LI X W, et al. A novel coronavirus from patients with pneumonia in China, 2019[J].The New England Journal of Medicine,2020,382(8): 727-733.
    [3]LU R J, ZHAO X, LI J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding[J].The Lancet,2020,395(10224): 565-574.
    [4]JIN Z M, DU X Y, XU Y C, et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors[J].Nature,2020,582(7811): 289-293.
    [5]HSU W C, CHANG H W, CHOU C Y, et al. Critical assessment of important regions in the subunit association and catalytic action of the severe acute respiratory syndrome coronavirus main protease[J].Journal of Biological Chemistry,2005,280(24): 22741-22748.
    [6]GHOSH A K, OSSWALD H L, PRATO G. Recent progress in the development of HIV-1 protease inhibitors for the treatment of HIV/AIDS[J].Journal of Medicinal Chemistry,2016,59(11): 5172-5208.
    [7]LI D C, LIU M S, HUANG Y G, et al. Identifying the molecular mechanics and binding dynamics characteristics of potent inhibitors to HIV-1 protease[J].Chemical Biology & Drug Design,2012,80(3): 440-454.
    [8]KITCHEN D B, DECORNEZ H, BAJORATH J, et al. Docking and scoring in virtual screening for drug discovery: methods and applications[J].Nature Reviews Drug Discovery,2004,3(11): 935-949.
    [9]DANIELS K G, SUO Y, OAS T G. Conformational kinetics reveals affinities of protein conformational states[J].Proceedings of the National Academy of Sciences,2015,112(30): 9352-9357.
    [10]RUVINSKY A M, KIRYS T, LLYA A, et al. Structure fluctuations and conformational changes in protein binding[J].Journal of Bioinformatics and Computational Biology,2012,10(2): 1241002.
    [11]SALMASO V, MORO S. Bridging molecular docking to molecular dynamics in exploring ligand-protein recognition process: an overview[J].Frontiers in Pharmacology,2018,9: 923.
    [12]LI D C, JI B H. Protein conformational transitions coupling with ligand interactions: simulations from molecules to medicine[J].Medicine in Novel Technology and Devices,2019,3: 100026.
    [13]HOLLINGSWORTH S A, DROR R O. Molecular dynamics simulation for all[J].Neuron,2018,99(6): 1129-1143.
    [14]YANG Y I, SHAO Q, ZHANG J, et al. Enhanced sampling in molecular dynamics[J].The Journal of Chemical Physics,2019,151(7): 070902.
    [15]BU B, TONG X, HU Y C, et al. N-terminal acetylation preserves α-synuclein from oligomerization by blocking intermolecular hydrogen bonds[J].ACS Chemical Neuroscience,2017,8(10): 2145-2151.
    [16]LI Z H, KONO H. Investigating the influence of arginine dimethylation on nucleosome dynamics using all-atom simulations and kinetic analysis[J].The Journal of Physical Chemistry B,2018,122(42): 9625-9634.
    [17]JO S, KIM T, LYER V G, et al. CHARMM-GUI: a web-based graphical user interface for CHARMM[J].Journal of Computational Chemistry,2008,29(11): 1859-1865.
    [18]LEE J, CHENG X, WEI S, et al. CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM simulations using the CHARMM36 additive force field[J].Journal of Chemical Theory and Computation,2015,12(1): 405-413.
    [19]GASTEIGER J, MARSILI M. A new model for calculating atomic charges in molecules[J].Tetrahedron Letters,1978,19(34): 3181-3184.
    [20]GASTEIGER J, MARSILI M. Iterative partial equalization of orbital electronegativity: a rapid access to atomic charges[J].Tetrahedron,1980,36(22): 3219-3228.
    [21]EBERHARDT J, SANTOS-MARTINS D, STEFANO F, et al. AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings[J].Journal of Chemical Information and Modeling,2021,61(8): 3891-3898.
    [22]TROTT O, OLSON A J. Autodock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading[J].Journal of Computational Chemistry,2010,31(2): 455-461.
    [23]ABRAHAM M J, MURTOLA T, HESS B, et al. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers[J].SoftwareX,2015,1/2: 19-25.
    [24]HUANG J, MACKERELL A J. CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data[J].Journal of Computational Chemistry,2013,34(25): 2135-2145.
    [25]BUSSI G, DONADIO D, PARRINELLO M. Canonical sampling through velocity rescaling[J].The Journal of Chemical Physics,2007,126(1): 014101.
    [26]BERENDSEN H J C, POSTMA J P M, GUNSTEREN W F, et al. Molecular dynamics with coupling to an external bath[J].The Journal of Chemical Physics,1984,81(8): 3684-3690.
    [27]HUMPHREY W, DALKE A, SCHULTEN K. VMD: visual molecular dynamics[J].Journal of Molecular Graphics,1996,14(1): 33-38.
    [28]PATRIKSSON A, VAN DER SPOEL D. A temperature predictor for parallel tempering simulations[J].Physical Chemistry Chemical Physics,2008,10(15): 2073-2077.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (784) PDF downloads(65) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return