Efficient calculation of rate constants: downhill versus uphill sampling.

Abstract

The classical transition state theory (TST), together with the notion of transmission coefficient, provides a useful tool for calculation of rate constants for rare events. However, in complex biomolecular reactions, such as protein folding, it is difficult to find a good reaction coordinate, so the transition state is ill-defined. In this case, other approaches are more popular, such as the transition interface sampling (TIS) and the forward flux sampling (FFS). Here, we show that the algorithms developed in the frames of TIS and FFS can be successfully applied, after a modification, for calculation of the transmission coefficient. The new procedure (which we call "downhill sampling") is more efficient in comparison with the traditional TIS and FFS ("uphill sampling") even if the reaction coordinate is bad. We also propose a new computational scheme that combines the advantages of TST, TIS, and FFS.