Recent Applications of Hybrid Ab Initio Quantum Mechanics – Molecular Mechanics Simulations to Biological Macromolecules

To understand the functional mechanisms of biological macromolecular systems, investigations of both the three-dimensional geometric and electronic structures are important. Accordingly, quantum mechanical (QM) calculations are essential to obtain the properties relevant to the electronic structures of the macromolecular systems. However, because of the high computational costs, only a few hundred atoms can be included in the usual ab initio QM calculations. Therefore, even though biological macromolecular systems include a huge number of atoms, isolated QM model calculations have been performed to date, in which only the reaction centres are considered. However, this may lead to serious misunderstandings of the properties relevant to the electronic structures of the macromolecular systems. To overcome these problems, the ab initio QM calculation is combined with a molecular mechanics (MM) calculation method; this is referred to as a QM/MM calculation. In this strategy, the QM calculation is adopted for the active site (QM regions), and for the remainder of the system, the MM calculation is adopted (MM regions). This QM/MM methodology was originally developed by Warshel and Levitt (Warshel&Levitt, 1976), and since their pioneering work, great progress has been made in the development of QM/MM algorithms and their applications to biological systems (Bruice&Kahn, 2000; Field, 2002; Field et al., 1990; Gao et al., 2006; Lin&Truhlar, 2007; Mulholland, 2005; Ryde, 2003; Senn&Thiel, 2007, 2009). In this chapter, we discuss some useful QM/MM schemes and their recent applications to analyze the functional mechanisms of biological macromolecular systems. Here, we will utilize three molecular systems as examples of applications of QM/MM calculations to biological macromolecules. We will also introduce the theoretical background to investigate the functional mechanisms in proteins, such as electron transfer.