How to turn the reaction coordinate into time

A simple Markov model of the TR passage, and a consideration that multiple crossings of the TR can contribute to the magnitude of an apparent rate constant, leads to a temporal interpretation of Φ. One useful aspect of this approach is that it allows us to consider TRs that are not parabolic and, importantly, to use experiments (the rate constants) to probe the overall shape of the TR barrier. Certainly, reaction mechanisms for protein conformational change are more complex than is encoded in the simple model. It is likely that the microscopic structural transitions of the TR are not obligatorily sequential. There may be multiple pathways over the separating barrier. Perturbations of the TR may change more than a single microscopic equilibrium constant. It still uncertain whether the sequential, Markov scheme for the TR is a sufficient approximation for some reactions, and, if not, whether this approach can be extended to incorporate more complex mechanisms of protein conformational change.