User:TheLarry/Notebook/Larrys Notebook/2009/08/06

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Fooling around with 148 Rate Constants

Ok i added in the ability to have different binding rate constants depending if the foot is in the front or back. Worse comes to worse i can make them the same. OK Time to Get Started! <-- Yeah that's an exclamation point mother fucker. That means it's on.

Reasoning

  • Block said that the diffusive step takes ~10μ seconds. So k for the step should be on the order of 1E5 in "Kinesin Motor Mechanics: Binding, Stepping, Tracking, Gating, and Limping"
  • Unbound kinesin binds very tightly to ADP according to Cross "Kinetic Mechanism of Kinesin"
    • Cross says that ATP binding in an unbound state is approximate to ATP binding in a bound state. So I think the idea is that these molecules will bind and unbind at the same rate. Meanwhile ADP will bind and hold it there.
    • Gilbert in "Pathway of Processive ATP Hydrolysis of Kinesin" gives a similar number as Cross for ATP release from unbound head.
    • ~.01 1/s for ADP unbinding
    • Cross gives ATP binding at ~4μ 1/Ms. He gives for bound to be ~2μ 1/Ms
    • Ma and Taylor say in 1995 "Kinetic mechanism of Kinesin Motor Domain" that ATPase activity is increased more than 1000 fold by finding to microtubules
  • With a step of 10,000 1/s this thing will fly back and forth. However it should bind to the MT after it steps forward. (or at least after a couple of sloshes back and forth). So a k of 5,000 1/s to bind will mean that 1/3 of the time it should bind. So possibly something like that then
    • And I want it to have a higher chance to bind in the front too. So that should be less than 5,000
    • SIDE NOTE: i should find some distance per time graphs of the processivity of kinesin so i can get an idea how often this molecule steps and binds. right now i have it stepping 3 times more than binding. 10,000 : 5,000
    • Also i think it should bind better when it is in front of ATP. That should be the best binding behavior.
    • Right now i have 5k for when the unbound foot is in front. 7k when the unbound foot is in front of ATP. 3k for unbound foot behind. 4k for unbound foot behind ATP.
      • The different values for ATP might be me just making sure this follows what i want it to.
  • Bound Empty in front binding ATP should be most likely to happen when the foot in back is ADP. This is one of the coopertivity shitticles.
    • Ma and Taylor in "Kinetic Mechanism of Kinesin Motor Domain" says that binding ATP should be 200 1/s. This number should be ATP concentration dependent, but i'll fix that later. Something like 4μ 1/Ms is what i remember for this. but i'll take 200 for now.
  • I agree with what i read yesterday that the best time for the kinesin to detach from the MT is with an ADP bound. This seems to be the weakest bind to MT of all the situations. These numbers will depend on the constraints of 140 steps before falling and ~1 sec before falling off. Plus this should follow the 99.3% chance of finishing a step. For now i'll have the number on the order of 1.
  • I haven't found anyone who studies the strain based on nucleotide states. Like which pulls harder empty or ATP. Front or back? All i know is that ATP can pull off ADP. And ADP allows empty to bind ATP. So i'll guess on the rest. empty is behind ATP. What does that mean? is ATP pulling empty to unbind? if it's symmetrical empty should not be able to bind ATP. let's go with symmetry for a bit.
  • According to Gilbert ATP becoming ADP-P is somewhere between 120 and 200 1/s.
  • ADP-P turning into ADP seems to be the limiting step with most people giving rate constants on the order of 10s.

Surprise Surprise my first try at numbers didn't work perfectly. I need a bit of a plan. Right now I want for the kinesin to detach after 100 steps. For this i'll fuck with the unbinding numbers.

At the end of the day it seems like i got some decent looking constants in there. All of my constants look like they fit into the literature except i have to multiply them by 8 to get the time correct (about 1 second before it falls off). But I thought this might happen so i can live with it for now. And because of this i am not gonna read a paper tonight or tomorrow morning. Suckett

Tomorrow I'll start working on my poster and if all goes well i can remain a day ahead of what i wanted. Yeah i got my simulation done within a week.


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