We moved on to investigate the observed protein-ligand interactions in the simulations. The most stable switch-II associated compounds, MRTX1133 and JDQ443, exhibit extremely stable (98-100%) interactions to Asp69, which is located on the opposite site of the pocket to position 12 (Figures ). Sotorasib and AZD4625 also interact with Asp69 but this is partially water-mediated, reflecting to the elevated switch-II flexibility associated with these compounds.