First, we paid our attention to the protein behavior and ligand stability in the simulations. The highest fluctuations of switch-II residues of KRAS are observed with sotorasib and AZD4625, whereas MRTX1133 and JDQ443 show the most stable protein in this region (Figure ). The systems with "compound 5B" and G12Si-1 fall in between the other in their switch-II behavior (Figure ). All ligands are relatively stable during the simulations based on ligand root-meansquare deviation (RMSD) values (Figure ). Generally, higher flexibility is perceived with