tetano
Editor, Senior Moderator
J Phys Chem Lett
. 2021 Jul 1;6252-6261.
doi: 10.1021/acs.jpclett.1c01548. Online ahead of print.
Regulation Mechanism for the Binding between the SARS-CoV-2 Spike Protein and Host Angiotensin-Converting Enzyme II
Haiyi Chen[SUP] 1 2 [/SUP], Yu Kang[SUP] 2 [/SUP], Mojie Duan[SUP] 1 [/SUP], Tingjun Hou[SUP] 2 3 [/SUP]
Affiliations
Abstract
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.
. 2021 Jul 1;6252-6261.
doi: 10.1021/acs.jpclett.1c01548. Online ahead of print.
Regulation Mechanism for the Binding between the SARS-CoV-2 Spike Protein and Host Angiotensin-Converting Enzyme II
Haiyi Chen[SUP] 1 2 [/SUP], Yu Kang[SUP] 2 [/SUP], Mojie Duan[SUP] 1 [/SUP], Tingjun Hou[SUP] 2 3 [/SUP]
Affiliations
- PMID: 34196550
- DOI: 10.1021/acs.jpclett.1c01548
Abstract
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.