Power\nStrokes in Molecular Motors: Predictive, Irrelevant,\nor Somewhere in Between?

For several decades,\nmolecular motor directionality has been rationalized\nin terms of the free energy of molecular conformations visited before\nand after the motor takes a step, a so-called power stroke mechanism\nwith analogues in macroscopic engines. Despite theoretical and experimental\ndemonstrations of its flaws, the power stroke language is quite ingrained,\nand some communities still value power stroke intuition. By building\na catalysis-driven motor into simulated numerical experiments, we\nhere systematically report on how directionality responds when the\nmotor is modified accordingly to power stroke intuition. We confirm\nthat the power stroke mechanism generally does not predict motor directionality.\nNevertheless, the simulations illustrate that the relative stability\nof molecular conformations should be included as a potential design\nelement to adjust the motor directional bias. Though power strokes\nare formally unimportant for determining directionality, we show that\npractical attempts to alter a power stroke have side effects that\ncan in fact alter the bias. The change in the bias can align with\nwhat power stroke intuition would have suggested, offering a potential\nexplanation for why the flawed power stroke mechanism can retain apparent\nutility when engineering specific systems.