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Silico analysis of interaction between full-length SARS-CoV2 S protein with human Ace2 receptor: Modelling, docking, MD simulation.
Biophys Chem. 2020 12; 267:106472.BC

Abstract

Many key residues, which mediate the interaction between SARS-CoV2 spike glycoprotein (S protein) and human ACE2 receptor, have been reviewed using the SARS-CoV2 S spike protein with human ACE2 complex. The initial SARS-CoV2 S protein and ACE2 protein complex structure is formed by RBD structure of SARS-CoV2 S protein and ACE2 protein. However, the cryo-EM structure study targeting SARS-Cov S protein with human ACE2 complex has shown that there exist different binding conformations during the binding process facing ACE2 protein. It suggests the interaction between SARS-CoV2 S spike protein complex might have different binding conformations, which request full-length of SARS-CoV2 S protein complex in the structure-functional analysis. In this study, we built a full-length SARS-CoV2 S protein with human ACE2 complex by computational methods. Residues K31, H34, E35 in ACE2 protein were showed both in our full-length model and RBD structure model, which recognized as critical residues in previous studies. Surprisingly, ACE2 residues E564, R559, N556 were only found participating in the interaction of our full-length model, which suggested the full-length model has bigger binding interface. This finding was further supported by the interaction network of full-length model and RBD model. Meanwhile, the method bias was taken into consideration. Eventually, the MM-PBSA results showed the full-length model had a stronger binding free energy (almost 5-fold) than the RBD structure model of SARS-CoV2 S spike protein complex. In computational level, we present a stronger binding model containing a full-length structure of SARS-CoV2 S protein with ACE2 complex.

Authors+Show Affiliations

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China. Electronic address: liruilanzhou@163.com.Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China.Key Laboratory of Tropical Biological Resources, Ministry of Education, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32916377

Citation

Rui, Li, et al. "Silico Analysis of Interaction Between Full-length SARS-CoV2 S Protein With Human Ace2 Receptor: Modelling, Docking, MD Simulation." Biophysical Chemistry, vol. 267, 2020, p. 106472.
Rui L, Haonan L, Wanyi C. Silico analysis of interaction between full-length SARS-CoV2 S protein with human Ace2 receptor: Modelling, docking, MD simulation. Biophys Chem. 2020;267:106472.
Rui, L., Haonan, L., & Wanyi, C. (2020). Silico analysis of interaction between full-length SARS-CoV2 S protein with human Ace2 receptor: Modelling, docking, MD simulation. Biophysical Chemistry, 267, 106472. https://doi.org/10.1016/j.bpc.2020.106472
Rui L, Haonan L, Wanyi C. Silico Analysis of Interaction Between Full-length SARS-CoV2 S Protein With Human Ace2 Receptor: Modelling, Docking, MD Simulation. Biophys Chem. 2020;267:106472. PubMed PMID: 32916377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Silico analysis of interaction between full-length SARS-CoV2 S protein with human Ace2 receptor: Modelling, docking, MD simulation. AU - Rui,Li, AU - Haonan,Li, AU - Wanyi,Chen, Y1 - 2020/09/03/ PY - 2020/07/15/received PY - 2020/08/19/revised PY - 2020/08/27/accepted PY - 2020/9/12/pubmed PY - 2020/12/15/medline PY - 2020/9/11/entrez KW - ACE2 KW - MD KW - MM-PBSA KW - SARS-CoV2 KW - Spike protein SP - 106472 EP - 106472 JF - Biophysical chemistry JO - Biophys Chem VL - 267 N2 - Many key residues, which mediate the interaction between SARS-CoV2 spike glycoprotein (S protein) and human ACE2 receptor, have been reviewed using the SARS-CoV2 S spike protein with human ACE2 complex. The initial SARS-CoV2 S protein and ACE2 protein complex structure is formed by RBD structure of SARS-CoV2 S protein and ACE2 protein. However, the cryo-EM structure study targeting SARS-Cov S protein with human ACE2 complex has shown that there exist different binding conformations during the binding process facing ACE2 protein. It suggests the interaction between SARS-CoV2 S spike protein complex might have different binding conformations, which request full-length of SARS-CoV2 S protein complex in the structure-functional analysis. In this study, we built a full-length SARS-CoV2 S protein with human ACE2 complex by computational methods. Residues K31, H34, E35 in ACE2 protein were showed both in our full-length model and RBD structure model, which recognized as critical residues in previous studies. Surprisingly, ACE2 residues E564, R559, N556 were only found participating in the interaction of our full-length model, which suggested the full-length model has bigger binding interface. This finding was further supported by the interaction network of full-length model and RBD model. Meanwhile, the method bias was taken into consideration. Eventually, the MM-PBSA results showed the full-length model had a stronger binding free energy (almost 5-fold) than the RBD structure model of SARS-CoV2 S spike protein complex. In computational level, we present a stronger binding model containing a full-length structure of SARS-CoV2 S protein with ACE2 complex. SN - 1873-4200 UR - https://www.unboundmedicine.com/medline/citation/32916377/Silico_analysis_of_interaction_between_full_length_SARS_CoV2_S_protein_with_human_Ace2_receptor:_Modelling_docking_MD_simulation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-4622(20)30180-0 DB - PRIME DP - Unbound Medicine ER -