Table 1.

Comparisons between PPI interfaces and binding sites

PPI interfaces	Binding sites
Target properties
Large surface area (1000‐6000 Å2)	Small surface (300‐1000 Å2) Hydrophobic
Preference for Trp (W), Tyr (Y), and Arg (R) as PPI hotspot residues; subpockets	Large volume (~ 260 Å3)
Shallow, flat, flexible	Pocket, cliff
Hydrophobic, featureless, undruggability	Diverse properties
Chemical space
MW ≥ 400	MW ≤ 500
LogP ≥ 4	LogP ≤ 500
HBA ≥ 4	HBA ≤ 10
Number of rings: ≥ 4	HBD ≤ 5
Ro4 Morelli’s rules	Lipinski’s Rule of 5 (Ro5)
Quantitative estimate of drug-likeness scores
QEPPI	QED