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Basic Characteristics of Mutations
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Mutation Site
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G339D |
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Mutation Site Sentence
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In both structures, Omicron partially exposes these mutations to the solvent: K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, G339D, and Y505H (shown as purple spheres). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RBD |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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Omicron |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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36694788
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Title
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Omicron mutations increase interdomain interactions and reduce epitope exposure in the SARS-CoV-2 spike
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Author
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Wieczor M,Tang PK,Orozco M,Cossio P
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Journal
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iScience
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Journal Info
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2023 Feb 17;26(2):105981
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Abstract
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Omicron BA.1 is a highly infectious variant of SARS-CoV-2 that carries more than thirty mutations on the spike protein in comparison to the Wuhan wild type (WT). Some of the Omicron mutations, located on the receptor-binding domain (RBD), are exposed to the surrounding solvent and are known to help evade immunity. However, the impact of buried mutations on the RBD conformations and on the mechanics of the spike opening is less evident. Here, we use all-atom molecular dynamics (MD) simulations with metadynamics to characterize the thermodynamic RBD-opening ensemble, identifying significant differences between WT and Omicron. Specifically, the Omicron mutations S371L, S373P, and S375F make more RBD interdomain contacts during the spike's opening. Moreover, Omicron takes longer to reach the transition state than WT. It stabilizes up-state conformations with fewer RBD epitopes exposed to the solvent, potentially favoring immune or antibody evasion.
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Sequence Data
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-
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