where ε HOMO and ε LUMO are the energies of the highest occupied and lowest unoccupied molecular orbitals. Unfortunately, employing the canonical HOMO and LUMO energies to calculate the electrophilicity index does not result in high predictability with respect to the reactivity of covalent inhibitors. Instead, Hermann et al. showed that by analyzing the highest occupied and lowest unoccupied orbitals and selecting those that are associated with the warhead (i.e., the left-hand side of the structures in Figure ), it is possible to calculate a warhead-associated electrophilicity index that strongly correlates with the reactivity of covalent inhibitors.