QM and QM/MM Simulations of Proteins

Molecular dynamics simulations of biomolecules have matured into powerful tools of structural biology. In addition to the commonly used empirical force field potentials, quantum mechanical descriptions are gaining popularity for structure optimization and dynamic simulations of peptides and proteins. In this chapter, we introduce methodological developments such as the QM/MM framework and linear-scaling QM that make efficient calculations on large biomolecules possible. We identify the most common scenarios in which quantum descriptions of peptides and proteins are employed, such as structural refinement, force field development, treatment of unusual residues, and predicting spectroscopic and exited state properties. The benefits and shortcomings of QM potentials, in comparison to classical force fields, are discussed, with special emphasis on the sampling problems of protein conformational space. Finally, recent examples of QM/MM calculations in light-sensitive membrane proteins illustrate typical applications of the reviewed methods.