Modeling chemical reactivity in complex systems: Insights from hybrid QM/MM MD simulations

The computational modeling of catalytic processes can provide important insights that can be exploited for their rationalization and optimization. However, modeling these processes often becomes a rather challenging task, especially if they take place in a complex environment, because it requires employing computational methods capable of accurately capturing the changes in electronic structure during chemical reactions and, at the same time, the influence of the surroundings, including the dynamical behavior. Hybrid quantum mechanical/molecular mechanical molecular dynamics (QM/MM MD) simulations offer a powerful tool that can be used to shed light on such processes, but their applications are often limited as only short time scales are accessible, in particular when employing first-principles electronic structure methods. The timescale limitation can be addressed by a diverse set of advanced simulation techniques, such as enhanced sampling methods and multiple time step acceleration, in combination with efficient simulation software frameworks, such as MiMiC. This article highlights the utility of QM/MM MD simulations combining multiple of these approaches in elucidating reaction mechanisms across a diverse set of chemical systems with biomedical and environmental relevance, illustrating how these methods provide key atomistic insights into complex chemical phenomena.