Flap structure within receptor binding domain of SARS-CoV-2 spike periodically obstructs hACE2 Binding subdomain bearing similarities to HIV-1 protease flap

被引:1
作者
Peters, Michael H. [1 ]
机构
[1] Virginia Commonwealth Univ, Richmond, VA 23284 USA
关键词
MOLECULAR-DYNAMICS;
D O I
10.1038/s41598-022-20656-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The SARS-CoV-2 prefusion spike protein is characterized by a high degree of flexibility and temporal transformations associated with its multifunctional behavior. In this study, we have examined the dynamics of the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein in detail. Its primary, binding subdomain with human Angiotensin Covering Enzyme II includes a highly conspicuous flap or loop that is part of a beta hairpin loop structural motif. Dynamic details of the RBD obtained through RMSF and Order Parameter calculations are consistent with structural details including the stability of "glue" points or dominant interaction energy residues of the RBD in the Up and Down states with its neighboring N-terminal domain (NTD) protomer. The RBD flap in the Up state protomer periodically obstructs the binding site on an approximate 70 ns time interval and is reminiscent of an HIV-1 protease polypeptide flap that opens and closes to modulate that enzymes activity. No claim is made here regarding the possible modulating role of the flap; however, the flap may be a potential site for therapeutic targeting aimed at keeping it in the closed state, as previously demonstrated in the inhibition of the HIV-1 protease polypeptide. The RBD primary binding subdomain is further shown to have not only similar dynamics but, also, an approximate 30% sequence similarity to the HIV-1 protease polypeptide.
引用
收藏
页数:7
相关论文
共 18 条
  • [1] NMR Order Parameter Determination from Long Molecular Dynamics Trajectories for Objective Comparison with Experiment
    Gu, Yina
    Li, Da-Wei
    Brueschweiler, Rafael
    [J]. JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2014, 10 (06) : 2599 - 2607
  • [2] HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations
    Hornak, V
    Okur, A
    Rizzo, RC
    Simmerling, C
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (04) : 915 - 920
  • [3] Software news and updates - CHARNIM-GUI: A web-based grraphical user interface for CHARMM
    Jo, Sunhwan
    Kim, Taehoon
    Iyer, Vidyashankara G.
    Im, Wonpil
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 2008, 29 (11) : 1859 - 1865
  • [4] A simple contact mapping algorithm form identifying potential peptide mimetics in protein-protein interaction partners.
    Krall, Alex
    Brunn, Jonathan
    Kankanala, Spandana
    Peters, Michael H.
    [J]. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2014, 82 (09) : 2253 - 2262
  • [5] Molecular Crowding Drives Active Pin1 into Nonspecific Complexes with Endogenous Proteins Prior to Substrate Recognition
    Luh, Laura M.
    Haensel, Robert
    Loehr, Frank
    Kirchner, Donata K.
    Krauskopf, Katharina
    Pitzius, Susanne
    Schaefer, Birgit
    Tufar, Peter
    Corbeski, Ivan
    Guentert, Peter
    Doetsch, Volker
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (37) : 13796 - 13803
  • [6] A GENERAL METHOD APPLICABLE TO SEARCH FOR SIMILARITIES IN AMINO ACID SEQUENCE OF 2 PROTEINS
    NEEDLEMAN, SB
    WUNSCH, CD
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1970, 48 (03) : 443 - +
  • [7] Transformations, Lineage Comparisons, and Analysis of Down-to-Up Protomer States of Variants of the SARS-CoV-2 Prefusion Spike Protein, Including the UK Variant B.1.1.7
    Peters, Michael H.
    Bastidas, Oscar
    Kokron, Daniel S.
    Henze, Christopher E.
    [J]. MICROBIOLOGY SPECTRUM, 2021, 9 (01): : 1 - 14
  • [8] Static all-atom energetic mappings of the SARS-Cov-2 spike protein and dynamic stability analysis of "Up" versus "Down" protomer states
    Peters, Michael H.
    Bastidas, Oscar
    Kokron, Daniel S.
    Henze, Christopher E.
    [J]. PLOS ONE, 2020, 15 (11):
  • [9] Peters Michael H, 2020, bioRxiv, DOI 10.1101/2020.05.12.091090
  • [10] Scalable molecular dynamics with NAMD
    Phillips, JC
    Braun, R
    Wang, W
    Gumbart, J
    Tajkhorshid, E
    Villa, E
    Chipot, C
    Skeel, RD
    Kalé, L
    Schulten, K
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 2005, 26 (16) : 1781 - 1802