Table 1.

Characteristics of Protein-Ligand Binding for Enzymes and Non-Enzymes in the Full Dataset.^a

Median	Low Affinity	High Affinity	Comparisonb
Physical	>250 nM	≤250 nM
Properties	ΔGbind > −9 kcal/mol	ΔGbind ≤−9 kcal/mol
Enzymes	1048 complexes	742 complexes	High-affinity ligands are 52% larger and more hydrophobic
ΔGbind	−6.6 kcal/mol	−10.9 kcal/mol
Sizec	21 atoms	32 atoms
BSA	305 Å2	419 Å2
ESA (%ESA)d	87 Å2 (22%)	144 Å2 (24%)
SlogP	0.3	2.4
−ΔGbind/atom	0.31 kcal/mol-atom	0.36 kcal/mol-atom
-ΔGbind/BSA	21 cal/mol-Å2	26 cal/mol-Å2
Non-Enzymes	234 complexes	190 complexes	Low-affinity ligands are three times more exposed and more hydrophilic
ΔGbind	−7.2 kcal/mol	−10.4 kcal/mol
Sizec	22 atoms	25 atoms
BSA	265 Å2	361 Å2
ESA (%ESA)d	118 Å2 (33%)	45 Å2 (11%)
SlogP	−2.2	1.5
−ΔGbind/atom	0.28 kcal/mol-atom	0.41 kcal/mol-atom
−ΔGbind/BSA	22 cal/mol-Å2	31 cal/mol-Å2
Comparisonb		Non-enzymes have 17% greater ligand efficiencies

^aValues presented are medians for each population.

^bAll differences noted in the comparisons sections have a statistical significance of >99.99% (p<0.0001).

^cLigand size is given in the number of non-hydrogen atoms.

^dPercent exposure is ESA/(ESA+BSA).