Cryptic pockets of proteins can offer invaluable allosteric drug-targeting opportunities . Although new in silico approaches are emerging to identify these pockets , more labor-intensive efforts are usually required for their detection. The latter was the case with KRAS, one of the key targets in cancer drug discovery . Decades of significant effort eventually resulted in the 2013 breakthrough, identifying a pocket that is not fully observable in KRAS crystal structures without ligand-induced changes . This pocket is located beneath the switch-II of KRAS and was hence named as the switch-II pocket (SII-P). KRAS is a highly dynamic protein, which is especially true when considering the highly flexible switch-II region . Therefore, the over 70 co-crystal structures of KRAS in complex with a SII-P small molecule binder available at the RCSB Protein Data Bank (PDB) have provided invaluable information on the dynamic behavior of this pocket. To date, KRAS SII-P targeting efforts have resulted in two clinically approved drugs sotorasib and adagrasib .