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

被引：3

作者：

Kugler, Valentina ^{[1
,2
]}

Lieb, Andreas ^{[3
]}

Guerin, Nathan ^{[4
]}

Donald, Bruce R. ^{[4
,5
,6
,7
]}

Stefan, Eduard ^{[1
,2
,8
,9
]}

Kaserer, Teresa ^{[10
]}

机构：

[1] Univ Innsbruck, Inst Biochem, Innsbruck, Austria

[2] Univ Innsbruck, Ctr Mol Biosci, Innsbruck, Austria

[3] Med Univ Innsbruck, Inst Pharmacol, Innsbruck, Austria

[4] Duke Univ, Dept Comp Sci, Durham, NC USA

[5] Duke Univ, Dept Biochem, Med Ctr, Durham, NC USA

[6] Duke Univ, Dept Chem, Durham, NC USA

[7] Duke Univ, Dept Math, Durham, NC USA

[8] Tyrolean Canc Res Inst TKFI, Innrain 66, A-6020 Innsbruck, Austria

[9] Univ Innsbruck, Inst Mol Biol, Innsbruck, Austria

[10] Univ Innsbruck, Inst Pharm Pharmaceut Chem, Innsbruck, Austria

来源：

COMMUNICATIONS BIOLOGY | 2023年 / 6卷 / 01期

基金：

奥地利科学基金会;

关键词：

STRUCTURAL BASIS; P16(INK4A) MUTATIONS; P53; MUTATIONS; CANCER; VARIANTS; MELANOMA; ALGORITHM;

D O I：

10.1038/s42003-023-05089-2

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Disruptor evaluates if mutations disrupt protein-protein and protein-DNA interactions and calculates relative probabilities that a specific mutation is formed to identify those with a high probability to become clinically relevant for carcinogenesis.

引用

页数：6

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Andreas Lieb
Nathan Guerin
Bruce R. Donald
Eduard Stefan
Teresa Kaserer
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