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, the 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 generally does not predict motor directionality.
Nevertheless, the simulations illustrate that the relative stability
of molecular conformations should be included as a potential design
element to adjust the motor directional bias. Though power strokes
are formally unimportant for determining directionality, we show that
practical attempts to alter a power stroke have side effects that
can in fact alter the bias. The change in the bias can align with
what power stroke intuition would have suggested, offering a potential
explanation for why the flawed power stroke mechanism can retain apparent
utility when engineering specific systems.