Empirical corrections and pair interaction energies in the fragment molecular orbital method

Highlights: • Efficient basis set superposition error corrections for FMO are developed. • Basis set corrections are built in pair interaction energy analysis. • A systematic study of interactions in a water cluster and protein-ligand complexes is conducted. The energy and analytic gradient are developed for FMO combined with the Hartree-Fock method augmented with three empirical corrections (HF-3c). The auxiliary basis set approach to FMO is extended to perform pair interaction energy decomposition analysis. The FMO accuracy is evaluated for several typical systems including 3 proteins. Pair interaction energies computed with different approaches in FMO are compared for a water cluster and protein-ligand complexes.