A mathematical model describing the mechanical kinetics of kinesin stepping

Abstract

The code for this work is written in Visual C# and is available by request from the authors.

Unbinding of Kinesin from Microtubule in the Strongly Bound States Enhances under Assisting Forces

“…This implies that the falling of the mean run length with rising force in both directions could attribute to only the rising frequency of backward stepping powered by ATP hydrolysis. This is consistent with the experimental observations in [4,5] and theoretical results in [20,22] showing that backward steppings are mainly generated by ATP hydrolysis. The mean backward displacement resynthesizing ATP is also found to be shorter under assisting forces (see Figure 1e), showing that the synthesis of ATP due to backward stepping is more likely to occur under resisting forces than under assisting forces.…”

“…then remarked that the experimental observations in rest on a misconception of the significance of dwell times before forward and backward steppings, and asserted that backward stepping could result in ATP synthesis. In addition, using the four‐state kinetic scheme, we recently modelled the stepping dynamics of kinesin, and in accordance with several sets of experimental and theoretical findings,,,, we showed that:, (i) the stall force is almost constant and [ATP]‐independent at ∼−7.3 pN, and (ii) backward stepping is mainly driven by ATP hydrolysis. Although experiments provided evidence that kinesin steps forward and backward in the direction of the applied force in the absence of ATP, due to the strain on the motor head generated by the force, in this paper, we study the ATP‐driven stepping of kinesin motor.…”

“…[38,39] By lowering [ATP] under low resisting forces, kinetic state (1) becomes the most probable state for the unbinding of kinesin from MT (see Figure 2b), due to a long waiting time for ATP binding, as reported in. [22,27] For assisting forces, our analysis suggests kinetic states (3) and (4) as the first and second most probable kinetic states for the detachment of kinesin from MT at saturating .com 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 [ATP] = 2 mM (see Figure 2a). Moreover, the detachment probabilities in the state (2), where kinesin shows high affinity for MT, [38,39] are enhanced.…”

“…In our previous studies, we developed a set of theoretical models for studying the mechanochemical kinetics underlying forward and backward steppings of a single kinesin ,,. On the basis of our findings in, and following the recent experiments in,, here we propose a theoretical model which takes into account the asymmetry of the force‐unbinding rate relation and describes how stepping kinetics of kinesin is affected by changing the direction of applied external force from resisting (negative) to assisting (positive); see Figure a. The model uses both analytical and computational methods.…”

Force Generated by Two Kinesin Motors Depends on the Load Direction and Intermolecular Coupling

“…[38] and used in Refs. [22,39,40], N is truncated when the occupancy probability of the most strained state falls below 1%, with a minimal effect on the calculations; see Fig. 3(b) and Ref.…”