Reaction coordinates and transition states in enzymatic catalysis

Enzymatic reactions are complex chemical processes taking place in complex dynamic environments. Theoretical characterization of these reactions requires the determination of the reaction coordinate and the transition state ensemble. This is not an easy task because many degrees of freedom may be involved in principle. We present recent efforts to find good enzymatic reaction coordinates and the implications of these findings in the interpretation of enzymatic efficiency. In particular, we analyze different strategies based on the use of minimum free energy paths and direct localization of the dividing surface on multidimensional free energy surfaces. Another strategy is based on the generation of reactive trajectories, using the transition path sampling method, from which transition state configurations can be harvested. Most of the applications carried out until now coincide to stress the change in the nature of the reaction coordinate, in terms of the participation of the chemical and environmental degrees of freedom, as the reaction advances. The degrees of freedom of the chemical system are dominant at the transition state while environmental participation can be more important at early or late stages of the process. WIREs Comput Mol Sci 2018, 8:e1329. doi: 10.1002/wcms.1329 This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Free Energy Methods Software > Simulation Methods