Inter-fragment interaction energy (IFIE) analysis estimates protein-ligand interactions with quantum (electronic) effects using a modest level of computational resources. Furthermore, by means of pair interaction energy decomposition analysis (PIEDA), the FMO interaction energy, ΔE FMO , is calculated as the sum of five energy terms: electrostatic (ΔE ES ), exchange repulsion (ΔE EX ), dispersion (ΔE DI ), charge transfer with higher-order mixed terms (ΔE CT + mix ), and solvation energy, as shown in equation ( ). This approach offers a detailed estimation of protein-ligand interactions in an implicit water, polarizable continuum model (PCM), that has been of great value in a range of drug discovery projects.