A systematic chemomechanical network model for the molecular motor kinesin is presented in this report. The network model is based on the nucleotide-dependent binding affinity of the heads to an microtubule (MT) and the asymmetries and similarities between the chemical transitions caused by the intramolecular strain between the front and rear heads. The network model allows for multiple chemomechanical cycles and takes into account all possible mechanical transitions between states in which one head is strongly bound and the other head is weakly bound to an MT. The results obtained from the model show the ATP-concentration dependence of the dominant forward stepping cycle and support a gated rear head mechanism in which the forward step is controlled by ATP hydrolysis and the resulting ADP-bound state of the rear head when the ATP level is saturated. When the ATP level is saturated, the energy from ATP hydrolysis is used to concentrate the chemical transition flux to a force-generating state that can produce the power stroke. In contrast, when the ATP level is low, the hydrolysis energy is consumed to avoid states in which the leading head is weakly bound to an MT and to inhibit frequent backward steps upon loading.
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