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Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein
Variants of SARS-CoV-2 keep emerging and causing new waves of COVID-19 around the world. Effective new approaches in drug development are based on the binding of agents, such as neutralizing monoclonal antibodies to a receptor-binding domain (RBD) of SARS-CoV-2 spike protein. However, mutations in R...
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| Published in: | Biomedicines 2022-12, Vol.10 (12), p.3233 |
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| Main Authors: | , , , , , , , , |
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| container_issue | 12 |
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| container_title | Biomedicines |
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| creator | Mamchur, Aleksandra A Stanishneva-Konovalova, Tatiana B Mokrushina, Yuliana A Abrikosova, Viktoria A Guo, Yu Zhang, Hongkai Terekhov, Stanislav S Smirnov, Ivan V Yaroshevich, Igor A |
| description | Variants of SARS-CoV-2 keep emerging and causing new waves of COVID-19 around the world. Effective new approaches in drug development are based on the binding of agents, such as neutralizing monoclonal antibodies to a receptor-binding domain (RBD) of SARS-CoV-2 spike protein. However, mutations in RBD may lower the affinity of previously developed antibodies. Therefore, rapid analysis of new variants and selection of a binding partner with high affinity is of great therapeutic importance. Here, we explore a computational approach based on molecular dynamics simulations and conformational clusterization techniques for the wild-type and omicron variants of RBD. Biochemical experiments support the hypothesis of the presence of several conformational states within the RBD assembly. The development of such an approach will facilitate the selection of neutralization drugs with higher affinity based on the primary structure of the target antigen. |
| doi_str_mv | 10.3390/biomedicines10123233 |
| format | article |
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The development of such an approach will facilitate the selection of neutralization drugs with higher affinity based on the primary structure of the target antigen.</description><identifier>ISSN: 2227-9059</identifier><identifier>EISSN: 2227-9059</identifier><identifier>DOI: 10.3390/biomedicines10123233</identifier><identifier>PMID: 36551988</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Affinity ; Amino acid sequence ; Amino acids ; Antibodies ; Binding proteins ; Cloning ; Computer applications ; Coronaviruses ; COVID-19 ; COVID-19 vaccines ; Drug development ; Drugs ; Experimental methods ; Glycoproteins ; Health aspects ; Hydrogen bonds ; Mate selection ; molecular dynamics ; Monoclonal antibodies ; Mutation ; Proteins ; receptor-binding domain ; Research methodology ; SARS-CoV-2 ; Severe acute respiratory syndrome coronavirus 2 ; Spike protein ; Viral proteins</subject><ispartof>Biomedicines, 2022-12, Vol.10 (12), p.3233</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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| ispartof | Biomedicines, 2022-12, Vol.10 (12), p.3233 |
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| source | Publicly Available Content Database; PubMed Central; Coronavirus Research Database |
| subjects | Affinity Amino acid sequence Amino acids Antibodies Binding proteins Cloning Computer applications Coronaviruses COVID-19 COVID-19 vaccines Drug development Drugs Experimental methods Glycoproteins Health aspects Hydrogen bonds Mate selection molecular dynamics Monoclonal antibodies Mutation Proteins receptor-binding domain Research methodology SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Spike protein Viral proteins |
| title | Conformational Dynamics of the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein |
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