Learning from failed steps of molecular walkers

Conventional kinesins are molecular motors that move in a hand-over-hand fashion along microtubules. Molecular walkers go through a series of coupled chemical and mechanical states when they take a step. In general, the motion of kinesins is unidirectional, confined to a single protofilament, and highly efficient. However, it is not perfect, and investigating which conditions lead to failed steps may provide insight into the mechanisms responsible for the proper function of motor proteins.

In recent work, we developed a mesoscopic model for kinesin stepping on a microtubule that can be simulated efficiently with Brownian dynamics simulations. Here, we focus on modeling the backward motion of kinesin under a retarding force. To this end, we modify the description of mechano-chemical states to include weakly attached states that allow detachment or backward sliding under specific conditions. To validate the model, we compare with kinesin data in the literature for stall force, kinesin detachment, and processivity and we also explore implications for side-stepping and obstacle encounters.