Efficient Polarizable\nQM/MM Using the Direct Reaction\nField Hamiltonian with Electrostatic Potential Fitted Multipole Operators

Electronic polarization\nand dispersion are decisive actors in determining\ninteraction energies between molecules. These interactions have a\nparticularly profound effect on excitation energies of molecules in\ncomplex environments, especially when the excitation involves a significant\ndegree of charge reorganization. The direct reaction field (DRF) approach,\nwhich has seen a recent revival of interest, provides a powerful framework\nfor describing these interactions in quantum mechanics/molecular mechanics\n(QM/MM) models of systems, where a small subsystem of interest is\ndescribed using quantum chemical methods and the remainder is treated\nwith a simple MM force field. In this paper we show how the DRF approach\ncan be combined with the electrostatic potential fitted (ESPF) multipole\noperator description of the QM region charge density, which significantly\nimproves the efficiency of the method, particularly for large MM systems,\nand for typical calculations effectively eliminates the dependence\non MM system size. We also show how the DRF approach can be combined\nwith fluctuating charge descriptions of the polarizable environment,\nas well as previously used atom-centered dipole-polarizability based\nmodels. We further show that the ESPF-DRF method provides an accurate\ndescription of molecular interactions in both ground and excited electronic\nstates of the QM system and apply it to predict the gas to aqueous\nsolution solvatochromic shifts in the UV/visible absorption spectrum\nof acrolein.