Power strokes in molecular motors: Predictive, irrelevant, or somewhere in between?

For several decades, molecular motor directionality has been rationalized in terms of the free energy of molecular conformations visited before and after the motor takes a step, a so-called power-stroke mechanism with analogues in macroscopic engines. Despite theoretical and experimental demonstrations of its flaws, power-stroke language is quite ingrained, and some communities still value power-stroke intuition. By building a catalysis-driven motor into simulated numerical experiments, we here systematically report on how directionality responds when the motor is modified accordingly to power-stroke intuition. We confirm that the power stroke mechanism does not generally predict the directionality. Still, the relative stability of molecular conformations can nevertheless be a useful design element that helps one alter the directional bias of a molecular motor. The ostensible effectiveness of power-stroke intuition is explained by the recognition that to target conformation stability, one must alter interactions between moieties of a molecular motor, and those altered interactions do not affect the power stroke in isolation. This can lead to apparent correlations between power stroke and directionality that one might leverage when engineering specific systems.