Insight into structural dynamics involved in activation mechanism of full length KRAS wild type and P-loop mutants.

ABSTRACT: KRAS protein is known to be frequently mutated in various cancers. The most common mutations being at position 12, 13 and 61. The positions 12 and 13 form part of the phosphate binding region (P-loop) of KRAS. Owing to mutation, the protein remains in continuous active state and affects the normal cellular process. Understanding the structural changes owing to mutations in GDP-bound (inactive state) and GTP-bound (active state) may help in the design of better therapeutics. To understand the structural flexibility due to the mutations specifically located at P-loop regions (G12D, G12V and G13D), extensive molecular dynamics simulations (24 μs) have been carried for both inactive (GDP-bound) and active (GTP-bound) structures for the wild type and these mutants. The study revealed that the l

SUBMITTER: Jani V 

PROVIDER: S-EPMC11379609 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature