Switching Channels in TPS: Rare events within rare events

Just as a spontaneous transition from one metastable state to another is a rare event in a molecular dynamics simulation, the transition from sampling one reaction channel to another can be a rare event in a transition path sampling simulation. Here we discuss how channel switching can be analyzed and enhanced in path sampling simulations. Several approaches will be presented, as well as applications to two biological systems: comparing two proposed mechanisms of a conformational transition in DNA, and comparing the dynamics of wild-type KRas with a cancer-causing mutant.