Optimization of Quantum Nuclei Positions with the Adaptive Nuclear-Electronic Orbital Approach.

The use of multicomponent methods has become increasingly popular over the last years. Under this framework, nuclei (commonly protons) are treated quantum mechanically on the same footing as the electronic structure problem. Under the use of atomic-centered orbitals, this can lead to some complications as the ideal location of the nuclear basis centers must be optimized. In this contribution, we propose a straightforward approach to determine the position of such centers within the self-consistent cycle of a multicomponent calculation, making use of individual proton charge centroids. We test the method on model systems including the water dimer, a protonated water tetramer, and a porphine system. Comparing to numerical gradient calculations, the adaptive nuclear-electronic orbital (NEO) procedure is able to converge the basis centers to within a few cents of an Ångström and with less than 0.1 kcal/mol differences in absolute energies. This is achieved in one single calculation and with a small added computational effort of up to 80% compared to a regular NEO- self-consistent field run. An example application for the human transketolase proton wire is also provided.

Nuclear Quantum Effects Made Accessible: Local Density Fitting in Multicomponent Methods.

The simulation of nuclear quantum effects (NQEs) is crucial for an accurate description of systems and processes involving light nuclei, such as hydrogen atoms. Within the last years, the importance of those effects has been highlighted for a vast range of systems with tremendous implications in chemistry, biology, physics, and materials sciences. However, while electronic structure theory methods have become routine tools for quantum chemical investigations, there is still a lack of approaches to address NQEs that are computationally accessible and straightforward to use. To address this, we present the first combination of the nuclear-electronic orbital Hartree-Fock approach with both local and density fitting approximations (LDF-NEO-HF). This results in a low-order scaling approach that enables the inclusion of NQEs for large systems within a fraction of a day and for small to medium size systems in minutes. Moreover, we demonstrate the qualitative accuracy and robustness of our approach to retrieve NQEs for three real-use cases motivated by chemical, biological, and materials science applications.

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome.

The 20S proteasome is a macromolecule responsible for the chemical step in the ubiquitin-proteasome system of degrading unnecessary and unused proteins of the cell. It plays a central role both in the rapid growth of cancer cells and in viral infection cycles. Herein, we present a computational study of the acid-base equilibria in an active site of the human proteasome (caspase-like), an aspect which is often neglected despite the crucial role protons play in the catalysis. As example substrates, we take the inhibition by epoxy- and boronic acid-containing warheads. We have combined cluster quantum mechanical calculations, replica exchange molecular dynamics, and Bayesian optimization of nonbonded potential terms in the inhibitors. In relation to the latter, we propose an easily scalable approach for the reevaluation of nonbonded potentials making use of the hybrid quantum mechanics molecular mechanics dynamics information. Our results show that coupled acid-base equilibria need to be considered when modeling the inhibition mechanism. The coupling between a neighboring lysine and the reacting threonine is not affected by the presence of the studied inhibitors.

A Review of Density Functional Models for the Description of Fe(II) Spin-Crossover Complexes.

Spin-crossover (SCO) materials have for more than 30 years stood out for their vast application potential in memory, sensing and display devices. To reach magnetic multistability conditions, the high-spin (HS) and low-spin (LS) states have to be carefully balanced by ligand field stabilization and spin-pairing energies. Both effects could be effectively modelled by electronic structure theory, if the description would be accurate enough to describe these concurrent influences to within a few kJ/mol. Such a milestone would allow for the in silico-driven development of SCO complexes. However, so far, the ab initio simulation of such systems has been dominated by general gradient approximation density functional calculations. The latter can only provide the right answer for the wrong reasons, given that the LS states are grossly over-stabilized. In this contribution, we explore different venues for the parameterization of hybrid functionals. A fitting set is provided on the basis of explicitly correlated coupled cluster calculations, with single- and multi-dimensional fitting approaches being tested to selected classes of hybrid functionals (hybrid, range-separated, and local hybrid). Promising agreement to benchmark data is found for a rescaled PBE0 hybrid functional and a local version thereof, with a discussion of different atomic exchange factors.