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

Valentina Kugler; Andreas Lieb; Nathan Guerin; Bruce R Donald; Eduard Stefan; Teresa Kaserer

doi:10.1038/s42003-023-05089-2

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

Commun Biol. 2023 Jul 13;6(1):720. doi: 10.1038/s42003-023-05089-2.

Authors

Valentina Kugler¹, Andreas Lieb², Nathan Guerin³, Bruce R Donald^{3

4

5

6}, Eduard Stefan^{1

7

8}, Teresa Kaserer⁹

Affiliations

¹ Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria.
² Institute of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
³ Department of Computer Science, Duke University, Durham, NC, USA.
⁴ Department of Biochemistry, Duke University Medical Center, Durham, NC, USA.
⁵ Department of Chemistry, Duke University, Durham, NC, USA.
⁶ Department of Mathematics, Duke University, Durham, NC, USA.
⁷ Tyrolean Cancer Research Institute (TKFI), Innrain 66, 6020, Innsbruck, Austria.
⁸ Institute of Molecular Biology, University of Innsbruck, Innsbruck, Austria.
⁹ Institute of Pharmacy/Pharmaceutical Chemistry, University of Innsbruck, Innsbruck, Austria. teresa.kaserer@uibk.ac.at.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

DNA* / genetics
Humans
Mutation
Proteins* / genetics

Substances

Proteins
DNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding