DISRUPTOR: Computational identification of oncogenic mutants disrupting protein interactions

We report an Osprey-based computational protocol to prospectively identify oncogenic mutations that act via disruption of molecular interactions. It is applicable to analyze both protein-protein and protein-DNA interfaces and has been validated on a dataset of clinically relevant mutations. In addition, it was used to predict previously uncharacterized patient mutations in CDK6 and p16 genes, which were experimentally confirmed to impair complex formation.