In silico comparative analysis of KRAS mutations at codons 12 and 13: Structural modifications of P-Loop, switch I&II regions preventing GTP hydrolysis.

ABSTRACT: KRAS mutation is prevalent in around 30% of all cancers and is an undruggable molecular target. Of seven mutations at codon 12 and 13, only one, the G12C mutant is finally proven to be druggable, as evidenced by the recent USFDA approval of sotorasib. Investigation of other small molecules targeting G12C and G12D are undergoing clinical trials. Understanding the fine structural details is a prerequisite to design specific inhibitors which also requires in depth molecular exploration. We used bioinformatics as a tool to analyze the KRAS protein's GTP (guanosine triphosphate) binding dynamics when mutated. KRAS undergoes significant conformational changes, affecting GTP binding conformation within the active site pocket of KRAS due to high torsional strains, hydrophobicity, and altered Switc

SUBMITTER: Gerber M 

PROVIDER: S-EPMC8810633 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature