Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions

We report an Osprey-based computational protocol to prospectively identify oncogenic mutations that act via disruption of molecular interactions. It is applicable to analyse both protein-protein and protein-DNA interfaces and it is validated on a dataset of clinically relevant mutations. In addition...

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Autores principales: Kugler, Valentina, Lieb, Andreas, Guerin, Nathan, Donald, Bruce R., Stefan, Eduard, Kaserer, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344873/
https://www.ncbi.nlm.nih.gov/pubmed/37443295
http://dx.doi.org/10.1038/s42003-023-05089-2
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author Kugler, Valentina
Lieb, Andreas
Guerin, Nathan
Donald, Bruce R.
Stefan, Eduard
Kaserer, Teresa
author_facet Kugler, Valentina
Lieb, Andreas
Guerin, Nathan
Donald, Bruce R.
Stefan, Eduard
Kaserer, Teresa
author_sort Kugler, Valentina
collection PubMed
description We report an Osprey-based computational protocol to prospectively identify oncogenic mutations that act via disruption of molecular interactions. It is applicable to analyse both protein-protein and protein-DNA interfaces and it is validated on a dataset of clinically relevant mutations. In addition, it is used to predict previously uncharacterised patient mutations in CDK6 and p16 genes, which are experimentally confirmed to impair complex formation.
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spelling pubmed-103448732023-07-15 Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions Kugler, Valentina Lieb, Andreas Guerin, Nathan Donald, Bruce R. Stefan, Eduard Kaserer, Teresa Commun Biol Article We report an Osprey-based computational protocol to prospectively identify oncogenic mutations that act via disruption of molecular interactions. It is applicable to analyse both protein-protein and protein-DNA interfaces and it is validated on a dataset of clinically relevant mutations. In addition, it is used to predict previously uncharacterised patient mutations in CDK6 and p16 genes, which are experimentally confirmed to impair complex formation. Nature Publishing Group UK 2023-07-13 /pmc/articles/PMC10344873/ /pubmed/37443295 http://dx.doi.org/10.1038/s42003-023-05089-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kugler, Valentina
Lieb, Andreas
Guerin, Nathan
Donald, Bruce R.
Stefan, Eduard
Kaserer, Teresa
Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions
title Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions
title_full Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions
title_fullStr Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions
title_full_unstemmed Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions
title_short Disruptor: Computational identification of oncogenic mutants disrupting protein-protein and protein-DNA interactions
title_sort disruptor: computational identification of oncogenic mutants disrupting protein-protein and protein-dna interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344873/
https://www.ncbi.nlm.nih.gov/pubmed/37443295
http://dx.doi.org/10.1038/s42003-023-05089-2
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