Chapter 11: QM/MM Methods for Simulating Enzyme Reactions

The application of combined quantum mechanics/molecular mechanics (QM/MM) methods to biological systems has matured since the pioneering works of Karplus, Levitt and Warshel in the 1970s. The field has benefited from recent advances in computer hardware and software, allowing the use of increasingly accurate quantum mechanical methods or longer timescales to be achieved in molecular dynamics (MD) simulations. This chapter highlights the role that QM/MM methods have played in furthering our understanding of issues such as a novel catalytic role found for methionine in phosphite dehydrogenase, antibiotic deactivation by β-lactamases, mechanistic understanding of HIV-1 reverse transcriptase and the role of transition state stabilisation in catalysis in chorismate mutase.