The any particle molecular orbital/molecular mechanics approach

A computational scheme is proposed to broaden the range of applications of multicomponent methodologies for the study of local properties of big molecular systems existing in the gas phase and in solvated environments. This scheme extends the any particle molecular orbital (APMO) approach in the quantum mechanics/molecular mechanics (QM/MM) framework. As a first assessment of the performance of the proposed approach, we estimate the proton affinities (PAs) of seventy amines in the gas phase and the proton binding energies (PBEs) in the gas phase and in an explicitly solvated environment of the sixty-one protons present in the chignolin protein. These calculations are performed with the QM/MM versions of the APMO second-order proton propagator (APMO-PP2) and the APMO extended Koopmans’ theorem (APMO-KT) approaches. Calculated PAs and PBEs show significant reductions in the computational effort with a reduced loss in accuracy. These results suggest that the APMO/MM scheme might be used as a low-cost multi-component alternative for studies of local properties in big molecular systems. Graphical Abstract QMMM regions and CPU times for the APMO/MM approach