Improved hydrogen bonding at the NDDO-type semiempirical quantum mechanical/molecular mechanical interface

A semiempirical quantum mechanical (QM)/molecular mechanical (MM) potential with reformulated QM core-MM charge interactions is introduced, specifically to more accurately model hydrogen bonding at the QM/MM interface. Application of this potential using the PM3 Hamiltonian shows improved prediction of geometry and interaction energy for hydrogen bonded small molecule complexes typical of biomolecular interactions, without significantly impacting the modeling of other interaction types. Using this potential, more quantitative prediction of interaction energies is also found at a protein-ligand interface. © 2009 American Chemical Society.