KRAS K104 modification affects the KRAS-GEF interaction and mediates cell growth and motility.

Mutant RAS genes play an important role in regulating tumors through lysine residue 104 to impair GEF-induced nucleotide exchange, but the regulatory role of KRAS K104 modification on the KRAS mutant remains unclear. Therefore, we simulated the acetylation site on the KRAS three-dimensional protein structure, including KRAS, KRAS and KRAS, and determined their trajectories and binding free energy with GEF. KRAS induced structural changes in the α2- and α3-helices, promoted KRAS instability and hampered GEF binding (ΔΔG = 6.