MTR3D-AF2: Expanding the coverage of spatially derived missense tolerance scores across the human proteome using AlphaFold2.
missense mutation
pathogenicity prediction
population variation
protein structure prediction
selective pressure
Journal
Protein science : a publication of the Protein Society
ISSN: 1469-896X
Titre abrégé: Protein Sci
Pays: United States
ID NLM: 9211750
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
revised:
24
06
2024
received:
17
12
2023
accepted:
26
06
2024
medline:
20
7
2024
pubmed:
20
7
2024
entrez:
20
7
2024
Statut:
ppublish
Résumé
The missense tolerance ratio (MTR) was developed as a novel approach to assess the deleteriousness of variants. Its three-dimensional successor, MTR3D, was demonstrated powerful at discriminating pathogenic from benign variants. However, its reliance on experimental structures and homologs limited its coverage of the proteome. We have now utilized AlphaFold2 models to develop MTR3D-AF2, which covers 89.31% of proteins and 85.39% of residues across the human proteome. This work has improved MTR3D's ability to distinguish clinically established pathogenic from benign variants. MTR3D-AF2 is freely available as an interactive web server at https://biosig.lab.uq.edu.au/mtr3daf2/.
Substances chimiques
Proteome
0
Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e5112Subventions
Organisme : National Health and Medical Research Council
ID : GNT1174405
Organisme : Victorian Government's Operational Infrastructure Support Program
Informations de copyright
© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
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