• DLPNO-CCSD(T)/SVP inter-fragment binding energies were drawn from the "Sum of INTER-fragment total energies" entry, found in the "INTER-vs INTRA-FRAGMENT TOTAL ENERGIES (Eh)" section in the LED outputs. As a sanity check, we verified that binding energies derived from subtracting the sum of "Intrafragment total energies" from the "total energy" for a given PL complex (both found in the same section in LED output) produce identical energetic values -as shown in the ESI. Note that different definitions for "binding energies" can be found in the literature (some actually correspond to the "interaction energies" mentioned in the introduction); in our case, the term simply corresponds to the difference in total energies between the super-system and its underlying protein and ligand fragments Note that whereas the nonempirical DLPNO-CCSD(T) method and LED approach are used for generating the data considered in this paper -other methods (such as those based on a perturbation theory formalism) may generally be used for similar purposes. It should also be mentioned that the above basis set and PNO domains may rightfully be considered inadequate for quantitatively-accurate electronic structure calculations (resulting in energetics found within 1 kcal/mol from a reliable reference level) of noncovalent interactions in vacuum. That being said, it should be stressed that accurate calculation of NCI energetics should not be recognized as one of the main goals of the current paper. Instead, we will focus on using the very basic information derived from LED calculations for predictive purposes.