Pan, XaoliangRosta, EdinaShao, Yihan2018-12-062018-12-062018-09-29Pan, X.; Rosta, E.; Shao, Y. Representation of the QM Subsystem for Long-Range Electrostatic Interaction in Non-Periodic Ab Initio QM/MM Calculations. Molecules 2018, 23, 2500.https://hdl.handle.net/11244/316285This paper is published as part of a thematic issue of Molecules on “Combined Quantum Mechanical and Molecular Mechanical Methods and Simulations”. http://www.mdpi.com/journal/molecules/special_issues/QMIn QM/MM calculations, it is essential to handle electrostatic interactions between the QM and MM subsystems accurately and efficiently. To achieve maximal efficiency, it is convenient to adopt a hybrid scheme, where the QM electron density is used explicitly in the evaluation of short-range QM/MM electrostatic interactions, while a multipolar representation for the QM electron density is employed to account for the long-range QM/MM electrostatic interactions. In order to avoid energy discontinuity at the cutoffs, which separate the short- and long-range QM/MM electrostatic interactions, a switching function should be utilized to ensure a smooth potential energy surface. In this study, we benchmarked the accuracy of such hybrid embedding schemes for QM/MM electrostatic interactions using different multipolar representations, switching functions and cutoff distances. For test systems (neutral and anionic oxyluciferin in MM (aqueous and enzyme) environments), the best accuracy was acquired with a combination of QM electrostatic potential (ESP) charges and dipoles and two switching functions (long-range electrostatic corrections (LREC) and Switch) in the treatment of long-range QM/MM electrostatics. It allowed us to apply a 10Å distance cutoff and still obtain QM/MM electrostatics/polarization energies within 0.1 kcal/mol and time-dependent density functional theory (TDDFT)/MM vertical excitation energies within 10−3 eV from theoretical reference values.Attribution-NonCommercial 4.0 Internationalelectrostaticsmultipolar expansionmultiscale modelingQM/MMArticle10.3390/molecules23102500