Open AccessRegulation Mechanism for the Binding between the SARS-CoV-2 Spike Protein and Host Angiotensin-Converting Enzyme II
Author(s) -
Haiyi Chen,
Yu Min Kang,
Mojie Duan,
Tingjun Hou
Publication year - 2021
Publication title -
the journal of physical chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.563
H-Index - 203
ISSN - 1948-7185
DOI - 10.1021/acs.jpclett.1c01548
Subject(s) - angiotensin converting enzyme 2 , enzyme , chemistry , binding site , coronavirus , receptor , binding domain , plasma protein binding , microbiology and biotechnology , mechanism (biology) , covid-19 , spike protein , biology , biochemistry , medicine , disease , infectious disease (medical specialty) , philosophy , epistemology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is mainly mediated through the interaction between the spike protein (S-pro) of the virus and the host angiotensin-converting enzyme II (ACE2). The attachment of heparan sulfate (HS) to S-pro is necessary for its binding to ACE2. In this study, the binding process of the receptor-binding domain (RBD) of S-pro to ACE2 was explored by enhanced sampling simulations. The free-energy landscape was characterized to elucidate the binding mechanism of S-pro to ACE2 with and without HS fragment DP4. We found that the stability of the T470-F490 loop and the hydrophobic interactions contributed from F486/Y489 in the T470-F490 loop of S-pro are quite crucial for the binding, which is enhanced by the presence of DP4. Our study provides valuable insights for rational drug design to prevent the invasion of SARS-CoV-2.