Quantum-Mechanical/Molecular-Mechanical (QM/MM) Simulations for Understanding Enzyme Dynamics

Quantum mechanics/molecular mechanics (QM/MM) methods have become widely used for computational modeling of enzyme structure and mechanism. In these approaches, a portion of the enzyme of great interest (e.g., where a chemical reaction is occurring) is treated with QM, whereas the surrounding region is treated with MM. A critical challenge with these methods is the choice of the region to partition into QM and which to treat with MM along with numerous practical choices that must be made at each step of the modeling procedure. Here, we attempt to simplify this process by describing the steps involved in preparing protein structures, choosing the appropriate QM region size and electronic structure methods, preparing all necessary input files, and troubleshooting common errors for QM/MM simulations of enzymes.