Transition state based replica exchange interface sampling (TS-RETIS)

Transition state theory (TST) is the most common computational approach to calculate rate constants. It requires determining the free energy profile along a well-chosen reaction coordinate. From this, based on the assumption that crossing the maximum of the free energy profile from the reactant state always results in a long-lived transition to the product state, the TST rate equation can be derived. The TST assumption is, however, generally not valid in complex systems, but TST can be corrected for correlated recrossing by a transmission coefficient calculation. This approach, also know as the reactive flux method (RFM), is practically feasible if the bare TST approximation is moderately off, ca. less than an order of magnitude. If this is not the case, path sampling could be favorable. Path sampling, e.g. by means of replica exchange transition interface sampling (RETIS), allows a direct determination of the rate constants without determining a free energy profile first. RETIS is exact and its efficiency is insensitive to the choice of reaction coordinate, which is an advantage in complex systems. Several studies have suggested ways to combine both approaches though most of them are either based on approximations or do not dramatically improve the efficiency compared to RFM. The approach that we developed, transition state based RETIS (TS-RETIS), is both exact and efficient, even if the transmission coefficient is extremely low.