[gmx-users] how to calculate kinetic constant?

Christopher Neale chris.neale at mail.utoronto.ca
Sat Oct 5 20:14:08 CEST 2013

If you want K_on and K_off, then I think you need to look at long-time equilibrium simulations or massively repeated simulations connected with a MSM. Beyond that, I believe that you will need to understand all of the important free energy barriers in all degrees of freedom (hard, to say the least).

Rajat: how are you going to compute kinetics from a PMF? Barriers in orthogonal degrees of freedom don't show up on your PMF but can greatly affect the kinetics. Even relatively minor roughness of the multidimensional free energy surface and off-pathway kinetic traps are going to affect the kinetics but not the PMF. Some people have tried to circumvent this limitation by using the PMF in addition to computing the local diffusion at each small section of the order parameter (e.g., http://www.nature.com/nnano/journal/v3/n6/full/nnano.2008.130.html ) but unless there is excellent sampling overlap and lots of transitions between all relevant states, I see this as a way to calculate an upper bound of rates that I think could easily be much slower. See, for example, http://pubs.acs.org/doi/abs/10.1021/jp045544s . Finally, I am not sure how rates can be usefully extracted from a non-equilibrium method like REMD.

Unless I missed it, the paper that David cites: http://pubs.acs.org/doi/abs/10.1021/ct400404q doesn't compute kinetics. 

Perhaps the OP can provide more information on what they are trying to obtain, exactly.


-- original message --

If you are looking at binding/unbinding as a function of temperature
(hopefully with REMD), you can use g_kinetics. If you are looking at
unbinding/binding events in a single simulation with temperature, etc
constant (no annealing), you will need to calculate binding probabilities,
from which you can back out a rate constant. A simple google search gave me
these papers (http://www.pnas.org/content/90/20/9547.full.pdf,

Of course, the best approach is to calculate the PMF and back out the rate
constant from the free energy. Hope that helps.

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