To guide the hit-to-lead optimization process. The qualitative and quantitative determination of interaction energy (kcal/mol), and bond type (electrostatic or van der Waals) and frequency around a residue are key descriptors for prioritizing bindings site residues. The 3D-geometric space surrounding each binding site residue accounts for how easy it is to form an interaction with such residue? Similarly, the chemical features of assessed residue can account for the strength and type of binding and how it can influence the ligand efficiency (LE); equation (2) 31 ? (e.g., the negative charge of an aspartic acid forming "electrostatic interactions" or the benzene ring of phenylalanine forming pi-pi-stacking and hydrophobic "van der Waals interactions").