Q61 mutant-mediated dynamics changes of the GTP-KRAS complex probed by Gaussian accelerated molecular dynamics and free energy landscapes.

ABSTRACT: Understanding the molecular mechanism of the GTP-KRAS binding is significant for improving the target roles of KRAS in cancer treatment. In this work, multiple replica Gaussian accelerated molecular dynamics (MR-GaMD) simulations were applied to decode the effect of Q61A, Q61H and Q61L on the activity of KRAS. Dynamics analyses based on MR-GaMD trajectory reveal that motion modes and dynamics behavior of the switch domain in KRAS are heavily affected by the three Q61 mutants. Information of free energy landscapes (FELs) shows that Q61A, Q61H and Q61L induce structural disorder of the switch domain and disturb the activity of KRAS. Analysis of the interaction network uncovers that the decrease in the stability of hydrogen bonding interactions (HBIs) of GTP with residues V29 and D30 induced

SUBMITTER: Chen J 

PROVIDER: S-EPMC8978876 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature