Effect of the QM Size, Basis Set and Polarisation on QM/MM Energy Decomposition Analysis

Herein, an Energy Decomposition Analysis (EDA) scheme extended to the framework of QM/MM calculations in the context of electrostatic and polarisable embeddings (QM/MM-EDA) is applied to assess the effect of the QM region size on the convergence of the different interaction energy components, nameyl, electrostatic, Pauli and polarisation, for cationic, anionic and neutral systems interacting with a strong polar environment (water). Significant improvements are found when the bulk solvent environment is described by a MM potential in the EDA scheme as compared to pure QM calculations that neglect bulk solvation. The predominant electrostatic interaction requires for sizeable QM regions. The results reported here show that it is necessary to include a surprisingly large number of water molecules in the QM region to obtain converged values for this energy term, contrary to most cluster models often employed in the literature. Both the improvement of the QM wavefunction by means of a larger basis set and the introduction of polarisation into the MM region through a polarisable embedding do not translate to a faster convergence with the QM region size, but lead to better results for the different interaction energy components.