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COSMIC Cancer Gene Census 3D database: understanding the impacts of mutations on cancer targets

Alsulami, AF; Torres, PHM; Moghul, I; Arif, SM; Chaplin, AK; Vedithi, SC; Blundell, TL; (2021) COSMIC Cancer Gene Census 3D database: understanding the impacts of mutations on cancer targets. Briefings in Bioinformatics , 22 (6) , Article bbab220. 10.1093/bib/bbab220. Green open access

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Abstract

Mutations in hallmark genes are believed to be the main drivers of cancer progression. These mutations are reported in the Catalogue of Somatic Mutations in Cancer (COSMIC). Structural appreciation of where these mutations appear, in protein-protein interfaces, active sites or deoxyribonucleic acid (DNA) interfaces, and predicting the impacts of these mutations using a variety of computational tools are crucial for successful drug discovery and development. Currently, there are 723 genes presented in the COSMIC Cancer Gene Census. Due to the complexity of the gene products, structures of only 87 genes have been solved experimentally with structural coverage between 90% and 100%. Here, we present a comprehensive, user-friendly, web interface (https://cancer-3d.com/) of 714 modelled cancer-related genes, including homo-oligomers, hetero-oligomers, transmembrane proteins and complexes with DNA, ribonucleic acid, ligands and co-factors. Using SDM and mCSM software, we have predicted the impacts of reported mutations on protein stability, protein-protein interfaces affinity and protein-nucleic acid complexes affinity. Furthermore, we also predicted intrinsically disordered regions using DISOPRED3.

Type: Article
Title: COSMIC Cancer Gene Census 3D database: understanding the impacts of mutations on cancer targets
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/bib/bbab220
Publisher version: https://doi.org/10.1093/bib/bbab220
Language: English
Additional information: © The Author(s) 2021. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Cancer Gene Census 3D, hallmark mutations, modelling cancer genes census, mutational analyses of cancer drug targets
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10142182
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