We extend for the first time a quantum mechanical energy decomposition analysis scheme based on deformation electron densities to a hybrid electrostatic embedding quantum mechanics/molecular mechanics framework. The implemented approach...

The intermolecular interactions established between anticancer drugs and lipid membranes play a key role in the permeation mechanism of the drugs inside the cells. Herein we extend a quantum mechanical energy decomposition analysis scheme based on deformation electron densities to a hybrid multiscale quantum mechanics/molecular mechanics (QM/MM) framework, and apply it to characterize the interactions between the cisplatin drug and a dioleyl-phosphatidylcholine lipid membrane. The interaction energy decomposition into electrostatic, induction, dispersion and Pauli repulsion contributions is performed for ensembles of geometries taken from molecular dynamics simulations to account for conformational sampling and, thus, obtain a distribution of each of the energy components. Contrary to a previous energy decomposition using force fields, it is evidenced that the electrostatic component is predominant in both polar and non-polar regions of the bilayer, and the repulsive component is strong when considered quantum mechanically, while being largely underestimated by the force field

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.

We present a toolkit that allows for the preparation of QM/MM input files from a conformational ensemble of molecular geometries. The toolkit can be used in command line, so that no programming experience is required, although it presents some features that can also be employed as a python application programming interface. We apply the toolkit in four situations in which different electronic-structure properties of organic molecules in the presence of a solvent or a complex biological environment are computed: the reduction potential of the nucleobases in acetonitrile, an energy decomposition analysis of tyrosine interacting with water, the absorption spectrum of an azobenzene derivative integrated into a voltage-gated ion channel, and the absorption and emission spectra of the luciferine/luciferase complex. These examples show that the toolkit can be employed in a manifold of situations for both the electronic ground state and electronically excited states. It also allows for the automatic correction of the active space in the case of CASSCF calculations on an ensemble of geometries, as it is shown for the azobenzene derivative photoswitch case.

We present a toolkit that allows for the preparation of QM/MM input files from a conformational ensemble of molecular geometries. The package is currently compatible with trajectory and topology files in Amber, CHARMM, GROMACS and NAMD formats, and has the possibility to generate QM/MM input files for Gaussian (09 and 16), Orca (≥4.0), NWChem and (Open)Molcas. The toolkit can be used in command line, so that no programming experience is required, although it presents some features that can also be employed as a python application programming interface. We apply the toolkit in four situations in which different electronic-structure properties of organic molecules in the presence of a solvent or a complex biological environment are computed: the reduction potential of the nucleobases in acetonitrile, an energy decomposition analysis of tyrosine interacting with water, the absorption spectrum of an azobenzene derivative integrated into a voltage-gated ion channel, and the absorption and emission spectra of the luciferine/luciferase complex. These examples show that the toolkit can be employed in a manifold of situations for both the electronic ground state and electronically excited states. It also allows for the automatic correction of the active space in the case of CASSCF calculations on an ensemble of geometries, as it is shown for the azobenzene derivative photoswitch case.