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

Abstract

Herein, an Energy Decomposition Analysis (EDA) scheme extended to the framework of QM/MM calculations in the context of electrostatic embeddings (QM/MM-EDA) including atomic charges and dipoles is applied to assess the effect of the QM region size on the convergence of the different interaction energy components, namely, electrostatic, Pauli, and polarization, 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 sizable 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 wave function by means of a larger basis set and the introduction of polarization into the MM region through a polarizable force field do not translate to a faster convergence with the QM region size, but they lead to better results for the different interaction energy components. The results obtained in this work provide insight into the effect of each energy component on the convergence of the solute−solvent interaction energy with the QM region size. This information can be used to improve the MM FFs and embedding schemes employed in QM/MM calculations of solvated systems.

QM/MM-Based Energy Decomposition Analysis Method for Large Systems

“…20 Similarly, the size of the QM region and its contribution to the convergence of EDA terms in QM/MM were also studied with respect to the solvation of small organic ions. 21 Here, we apply the GKS-EDA(QM/MM) study with different MM force fields for a system that includes a hydronium ion in water. Figure 5 shows the computational results of GKS-EDA(QM/MM) for H 3 O + ••• water interactions with various force fields and MM programs.…”

Intramolecular and intermolecular hole delocalization rules the reducer character of isolated nucleobases and homogeneous single-stranded DNA

“…Solvent effects were introduced with the ALPB model, 78 suitable for XTB. Although the inclusion of water molecules in the QM region could lead to PCCP Paper more reliable results, a very large number of water molecules could be needed to obtain converged results, 79 making the calculations computationally unfeasible. In addition, previous computational work has shown that the use of implicit solvation provides accurate oxidation potentials for the nucleobases.…”

Atoms in molecules in real space: a fertile field for chemical bonding

“…10). 218 Hence, IQA and other EDAs 220 could help in the diagnosis of QM/MM methodological problems and in the evaluation of possible solutions.…”