Optimal flexibility for conformational transitions in macromolecules

Conformational transitions in macromolecular complexes often involve the reorientation of leverlike structures. Using a simple theoretical model, we show that the rate of such transitions is drastically enhanced if the lever is bendable, e.g., at a localized hinge. Surprisingly, the transition is fastest with an intermediate flexibility of the hinge. In this intermediate regime, the transition rate is also least sensitive to the amount of "cargo" attached to the lever arm, which could be exploited by molecular motors. To explain this effect, we generalize the Kramers-Langer theory for multidimensional barrier crossing to configuration-dependent mobility matrices.