TCIs enact specificity and irreversible binding through a combination of covalent and noncovalent interactions at their protein's target site. Although non-covalent interactions make up the majority of contacts between a TCI and the binding pocket residues of the protein, target engagement via covalent bond formation (kinact) increases drugging efficiency (KI) by prolonging duration of action and increasing the degree of protein-drug occupancy in some cases de-coupling PK-PD , creating an opportunity to target shallow binding sites of challenging targets and improving selectivity towards target, target isoforms and diseaselinked mutants. Given these appealing features, development of new tools to support the rational design of TCIs has become an indispensable task.