Computational studies of anaplastic lymphoma kinase mutations reveal common mechanisms of oncogenic activation.

ABSTRACT: Kinases play important roles in diverse cellular processes, including signaling, differentiation, proliferation, and metabolism. They are frequently mutated in cancer and are the targets of a large number of specific inhibitors. Surveys of cancer genome atlases reveal that kinase domains, which consist of 300 amino acids, can harbor numerous (150 to 200) single-point mutations across different patients in the same disease. This preponderance of mutations-some activating, some silent-in a known target protein make clinical decisions for enrolling patients in drug trials challenging since the relevance of the target and its drug sensitivity often depend on the mutational status in a given patient. We show through computational studies using molecular dynamics (MD) as well as enhanced samplin

SUBMITTER: Patil K 

PROVIDER: S-EPMC7958353 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature