Partitioning of the Vibrational Free Energy

Abstract

Vibrational energies are partitioned into the contributions of molecular parts called segments, for instance, residues in proteins. The fragment molecular orbital method is used to facilitate vibrational calculations of large systems at the DFTB and HF-3c levels. The vibrational analysis is combined with the partitioning of the electronic energy, yielding free-energy contributions of segments to the binding energy, pinpointing hot spots for drug discovery and other studies. The analysis is illustrated on two protein–ligand complexes in solution.