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Anchor-Locker Binding Mechanism of the Coronavirus Spike Protein to Human ACE2: Insights from Computational Analysis.
Cong, Yalong; Feng, Yinghui; Ni, Hui; Zhi, Fengdong; Miao, Yulu; Fang, Bohuan; Zhang, Lujia; Zhang, John Z H.
Afiliação
  • Cong Y; Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
  • Feng Y; Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
  • Ni H; College of Food and Biology Engineering, Jimei University, Xiamen, Fujian 361021, China.
  • Zhi F; Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
  • Miao Y; Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
  • Fang B; Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
  • Zhang L; Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
  • Zhang JZH; NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China.
J Chem Inf Model ; 61(7): 3529-3542, 2021 07 26.
Article em En | MEDLINE | ID: mdl-34156227
COVID-19 has emerged as the most serious international pandemic in early 2020 and the lack of comprehensive knowledge in the recognition and transmission mechanisms of this virus hinders the development of suitable therapeutic strategies. The specific recognition during the binding of the spike glycoprotein (S protein) of coronavirus to the angiotensin-converting enzyme 2 (ACE2) in the host cell is widely considered the first step of infection. However, detailed insights on the underlying mechanism of dynamic recognition and binding of these two proteins remain unknown. In this work, molecular dynamics simulation and binding free energy calculation were carried out to systematically compare and analyze the receptor-binding domain (RBD) of six coronavirus' S proteins. We found that affinity and stability of the RBD from SARS-CoV-2 under the binding state with ACE2 are stronger than those of other coronaviruses. The solvent-accessible surface area (SASA) and binding free energy of different RBD subunits indicate an "anchor-locker" recognition mechanism involved in the binding of the S protein to ACE2. Loop 2 (Y473-F490) acts as an anchor for ACE2 recognition, and Loop 3 (G496-V503) locks ACE2 at the other nonanchoring end. Then, the charged or long-chain residues in the ß-sheet 1 (N450-F456) region reinforce this binding. The proposed binding mechanism was supported by umbrella sampling simulation of the dissociation process. The current computational study provides important theoretical insights for the development of new vaccines against SARS-CoV-2.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicoproteína da Espícula de Coronavírus / COVID-19 Limite: Humans Idioma: En Revista: J Chem Inf Model Assunto da revista: INFORMATICA MEDICA / QUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicoproteína da Espícula de Coronavírus / COVID-19 Limite: Humans Idioma: En Revista: J Chem Inf Model Assunto da revista: INFORMATICA MEDICA / QUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China