Quantum Mechanical/Molecular Mechanical (QM/MM) Studies of Enzymes

Computational methods are presented for modeling the catalytic center of an enzyme and calculating the energy associated with given molecular geometry. First, an introduction to general theory is given, including a brief discussion of quantum mechanics (QM), molecular mechanics (MM), and hybrid QM/MM, a standard approach that divides the system into a region requiring a description of the electronic structure (QM) and a remainder that can be considered a perturbation (MM) to the system. Next, the nitrogenase enzyme will be used as a sample system to explain in detail how modeling is carried out. This discussion will review the broken symmetry (BS) approach within DFT, a computational approach that describes the spin states of multiple Fe centers. The review concludes with a discussion of machine learning (ML) and the training of a neural network (NN) potential based on QM calculations.