In high probabilistic cases of ligandable covalent sites, binding of a covalent small molecule on a protein site is expected to induce structural change and potential opening or enlargement of a ligandable pocket or ostensibly a surface site. These structural transformations can give rise to discovery of hidden ligandable sites on proteins. Certainty around whether a previously unreported cavity detected in a conformational state as a false positive or, yet an undiscovered cryptic site is questionable. However, it is often possible to distinguish between superficial PPIlike sites and a buried cryptic binding site. In the past decade, many PPIs which once considered "undruggable" have now been successfully targeted by drug-like molecules . Protein surface cavities and novel ligandable pockets are revealed from loop motions, secondary structure element motions and changes, and interdomain motions that increase SASA on the target. It is imaginable that such perturbations cause exposure of covalently reactive residues that may otherwise be buried as reported for most covalent cysteine sites. This may give rise to indefinite estimates for setting a proximity distance threshold between covalent residue and pocket (Figure , Suppl. Figure ). Notably, the power of the advanced covalent ligandability assessment platform is well demonstrated by its high detection scores on covalent sites in the apo-covPDB dataset including those which are buried (Suppl. Table ) as well as in the cryptic-PDB dataset. Compared with a simplistic distance-based simplistic approach, the advanced ligandability assessment platform showcased an improved detection rate on missed cryptic-PDBs by 8-fold (33.6% vs 4.1%, Figure ). This indicates that the advanced platform is able to capture a diversity of conformational changes that lead to formation of cryptic pockets while maintaining a comparable detection rate of false-positives sites with the simplistic ligandability assessment platform (Suppl. Figure ).