Conformational selection and induced fit as a useful framework for molecular motor mechanisms

Abstract The linkage between macromolecular binding and conformational change that is ubiquitous in biological molecules can be understood in the context of the mechanisms of conformational selection and induced fit. Here, we explore mappings between these mechanisms of ligand binding and those underlying the translocation of molecular motors and the nucleic acid unwinding of helicases. The mechanism of biased motion exhibited by molecular motors is typically described as either a thermal ratchet or a power-stroke and nucleic acid helicases are characterized by either active or passive unwinding mechanisms. We posit that both Brownian ratchet translocation and passive unwinding are examples of conformational selection and that both power-stroke translocation and active unwinding are examples of induced fit. Furthermore, in ligand-binding reactions, both conformational selection and induced fit may exist in parallel leading to a ligand-dependent flux through the different mechanistic pathways. Given the mappings we describe, we propose that motors may be able to function via parallel ratchet and stroke mechanisms and that helicases may be able to function via parallel active and passive mechanisms.