This FMOPhore algorithm delivers an insight into the quantitative structure-activity relationship (QSAR) between bound molecules and the protein complex. It can also provide defined strategies for fragment growing approaches to maximize ligand efficiency (LE) by prioritizing target Hotspot residues. We have demonstrated that the growing of small molecules in the direction of key hotspot residues in the binding site can lead to better LE and potency of lead compounds with respect to growing molecules without a predetermined strategy. Similarly, we have highlighted how FMOPhore can be used to drive selective design in kinases.