Quantum Mechanical/Molecular Mechanical Approaches for the Investigation of Chemical Systems – Recent Developments and Advanced Applications

Hybrid quantum mechanical/molecular mechanical methods – or QM/MM – comprise a particularly successful but highly challenging approach in computational chemistry. In this theoretical framework the system of interest is separated into (at least) two subregions: atoms in the chemically most relevant zone are treated by means of an adequate quantum mechanical (QM) description, while more efficient empirical potential models commonly referred to as molecular mechanical (MM) or force field (FF) methods are considered sufficiently accurate to represent the remaining part of the system. The foundation of this well established methodology was laid as early as the 1970ies by the fundamental methodical developments made by the Nobel laureates Martin Karplus, Michael Levitt and Arieh Warshel in the context of organic and biochemical studies. These contributions have been termed ground-breaking in that they managed to make Newton’s classical physics work side-by-side with the fundamentally different quantum physics (The Royal Swedish Academy of Sciences, Nobel Prize 2013 – Press release). This statement not only provides evidence of the major achievements resulting from this area of research but highlights the challenging nature of this novel development, requiring detailed expertise in both quantum chemical approaches and force field methods to enable the simultaneous application to a single chemical system.

Five decades after the foundation of these methodologies QM/MM approaches proved as a versatile and general framework to model exciting and challenging phenomena in physical and chemical sciences. In particular the combination of this successful strategy with other theoretical approaches such has simulation methods based on statistical mechanics or algorithms designed to characterize the underlying potential energy landscape greatly enhanced the scope but at the same time the complexity of this theoretical framework. For this reason research focused at extending and improving the capacities of this simulation strategy is still an active field in theoretical/computational chemistry, resulting in a broad range of highly specialized approaches further improving the applicability, accuracy and efficiency of the QM/MM methodology. As a consequence today’s application are not limited to the regime of (bio)organic systems but cover investigations of liquid and solid-state systems relevant to both life and material sciences as well.

This article collection aims to present an overview of present research activities focused on development and application of modern QM/MM formulations to demonstrate the broad range of capabilities of this celebrated methodology. Original research articles describing novel, methodical innovations in the field of QM/MM comprise welcome contributions as well as advanced applications to challenging research questions. Opinion articles and (mini)reviews are also of interest for this article collection, if they fit within the focus of the Research Topic.