Reconceptualizing kinesin＇s working cycle as separate chemical and mechanical processes

The biomolecular motor kinesin uses chemical energy released from a fuel reaction to generate di- rectional movement and produce mechanical work. The underlying physical mechanism is not fully understood yet. To analyze the energetics of the motor, we reconceptualize its chemomechanical cy- cle in terms of separate fuel reaction and work production processes and introduce a thermodynamic constraint to optimize the cycle. The model predicts that the load dependences of the motor＇s veloc- ity, stepping ratio, and dwell time are determined by the mechanical parameters of the motor-track system rather than the fuel reaction rate. This behavior is verified using reported experimental data from wild-type and elongated kinesins. The fuel reaction and work production processes indicate that kinesin is driven by switching between two chemical states, probably following a general pattern for molecular motors. The comparison with experimental data indicates that the fuel reaction processes are close to adiabatic, which is important for efficient operation of the motor. The model also suggests that a soft, short neck linker is important for the motor to maintain its load transport velocity.