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Mechanistic Origin of Different Binding Affinities of SARS-CoV and SARS-CoV-2 Spike RBDs to Human ACE2.
Zhang, Zhi-Bi; Xia, Yuan-Ling; Shen, Jian-Xin; Du, Wen-Wen; Fu, Yun-Xin; Liu, Shu-Qun.
Afiliación
  • Zhang ZB; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China.
  • Xia YL; Yunnan Key Laboratory of Stem Cell and Regenerative Medicine and Biomedical Engineering Research Center, Kunming Medical University, Kunming 650500, China.
  • Shen JX; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China.
  • Du WW; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China.
  • Fu YX; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China.
  • Liu SQ; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China.
Cells ; 11(8)2022 04 09.
Article en En | MEDLINE | ID: mdl-35455955
The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (RBDCoV2) has a higher binding affinity to the human receptor angiotensin-converting enzyme 2 (ACE2) than the SARS-CoV RBD (RBDCoV). Here, we performed molecular dynamics (MD) simulations, binding free energy (BFE) calculations, and interface residue contact network (IRCN) analysis to explore the mechanistic origin of different ACE2-binding affinities of the two RBDs. The results demonstrate that, when compared to the RBDCoV2-ACE2 complex, RBDCoV-ACE2 features enhanced dynamicsand inter-protein positional movements and increased conformational entropy and conformational diversity. Although the inter-protein electrostatic attractive interactions are the primary determinant for the high ACE2-binding affinities of both RBDs, the significantly enhanced electrostatic attractive interactions between ACE2 and RBDCoV2 determine the higher ACE2-binding affinity of RBDCoV2 than of RBDCoV. Comprehensive comparative analyses of the residue BFE components and IRCNs between the two complexes reveal that it is the residue changes at the RBD interface that lead to the overall stronger inter-protein electrostatic attractive force in RBDCoV2-ACE2, which not only tightens the interface packing and suppresses the dynamics of RBDCoV2-ACE2, but also enhances the ACE2-binding affinity of RBDCoV2. Since the RBD residue changes involving gain/loss of the positively/negatively charged residues can greatly enhance the binding affinity, special attention should be paid to the SARS-CoV-2 variants carrying such mutations, particularly those near or at the binding interfaces with the potential to form hydrogen bonds and/or salt bridges with ACE2.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo / Glicoproteína de la Espiga del Coronavirus / Enzima Convertidora de Angiotensina 2 / SARS-CoV-2 Límite: Humans Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo / Glicoproteína de la Espiga del Coronavirus / Enzima Convertidora de Angiotensina 2 / SARS-CoV-2 Límite: Humans Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza