Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon

Using protein structure to predict function, interactions, and evolutionary history is still an open challenge, with existing approaches relying extensively on protein homology and families. Here, we present Machaon, a data-driven method combining orientation invariant metrics on phi-psi angles, int...

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Published inCommunications biology Vol. 6; no. 1; p. 752
Main Authors Kakoulidis, Panos, Vlachos, Ioannis S, Thanos, Dimitris, Blatch, Gregory L, Emiris, Ioannis Z, Anastasiadou, Ema
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 19.07.2023
Nature Publishing Group UK
Nature Portfolio
Subjects
ACE2
Angiogenesis
Angiotensin-converting enzyme 2
Binding Sites
Bioinformatics
Biology
Biotechnology
Computer Science
COVID-19
Homology
Humans
Life Sciences
Meta-analysis
Mimicry
Monomers
Protein structure
Proteins
Receptors, Virus - metabolism
SARS-CoV-2 - genetics
SARS-CoV-2 - metabolism
Severe acute respiratory syndrome coronavirus 2
Spike protein
Structure-function relationships
Ubiquitination
Virus attachment
Bioinformatics
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Summary:Using protein structure to predict function, interactions, and evolutionary history is still an open challenge, with existing approaches relying extensively on protein homology and families. Here, we present Machaon, a data-driven method combining orientation invariant metrics on phi-psi angles, inter-residue contacts and surface complexity. It can be readily applied on whole structures or segments-such as domains and binding sites. Machaon was applied on SARS-CoV-2 Spike monomers of native, Delta and Omicron variants and identified correlations with a wide range of viral proteins from close to distant taxonomy ranks, as well as host proteins, such as ACE2 receptor. Machaon's meta-analysis of the results highlights structural, chemical and transcriptional similarities between the Spike monomer and human proteins, indicating a multi-level viral mimicry. This extended analysis also revealed relationships of the Spike protein with biological processes such as ubiquitination and angiogenesis and highlighted different patterns in virus attachment among the studied variants. Available at: https://machaonweb.com .
Bibliography:ObjectType-Article-2
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ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-023-05076-7