The correlation ratchet: a novel mechanism for generating directed motion by ATP hydrolysis

Progressive enzymes are macromolecules which hydrolyze ATP while moving unidirectionally along a linear macromolecular “track”. Examples include motor molecules such as myosin, kinesin and dynein, RNA and DNA polymerases, and chaperonins. We propose a specific mechanical model for transduction of phosphate bond energy during ATP hydrolysis into directed motion. This model falls within the class we call “Brownian ratchets” since the model cannot function without the Brownian motion and since it derives its directionality from the rectification of such motion. (Peskin et al., 1994; Peskin et al., 1993; Simon et al., 1992). The model depends on two features of the motor system. First, there is a molecular asymmetry in the binding between the motor and its track which determines the direction the motor will move (Magnasco, 1993). Second, the nucleotide hydrolysis cycle pumps energy into the system by providing an alternating sequence of strong and weak binding states. The novelty of this mechanism is how these effects of ATP hydrolysis conspire to bias the Brownian motion of the motor. Removing either feature (alternation or asymmetry), or removing the thermal motion of the enzyme eliminates the transduction of the chemical cycle into directed motion. We call this mechanism a “correlation ratchet”, since its operation depends upon a correlation between the spatial position of the molecular motor and its binding state (strong/weak). When this correlation is lost the motor ceases to function (Feynman et al., 1963). We first present the model equations, and then supply an intuitive explanation for how the ratchet works.