Kinesin-1 Kinetics and Stochastic Simulation Overview

This is a simplified diagram of the software used in this simulation. This was programmed in Labview 7.1. The sub.vi’s (which are functions in Labview programming) labeled ―k’s next states‖ finds the rate constants for the head to tranistion to another state. This .vi allows for the heads to interact through their rate constants. The sub.vi labeled ―Choose New State‖ is the Monte Carlo portion of the program that finds random times for each transition and then chooses the transition that occurs in the shortest time 1 . The state shown at the top—empty head bound to the microtuble behind an unbound ADP head—can transition to seven different states. The current state, an empty head bound to the microtubule behind a head unbound to the microtubule with ADP attached to the head has seven possible states it can become. The green line shows the most probable transition which is ATP binding to the empty head. The simulation allows for all of these transitions though the probability can be low for some of them. In our agentbased simulation, we use a diffusive search as opposed to a lever arm model. The diffusion of the head from front/back has a rate constant of 1000 s -1 . These histograms show the consequences of varying on and off rates of kinesin heads binding and unbinding from the microtubule. We ran these experiments to get a qualitative idea of how osmotic stress or chemical denaturants may modify kinesin behavior. The red plots in this figure represents kinesin under normal conditions. The gray plot may indicate what