[RASMB] k_off rate

[SE Halford, Biochemistry]

Sorry, but I disagree strongly with Allen Minton's assertion that 
protein-protein association rates have "very similar bimolecular 
association rate constants (say within a factor of 3 or so).  I seem to 
remember something on the order of 10^5 mol^-1 sec^-1".
The protein-protein association rates reported in the literature vary from 
10^10 M^-1.s^-1 down to around 10^4 M^-1.s^-1.  The high numbers are almost 
all measured in low salt buffers, conditions where electrostatic effects 
overwhelm the "Smoluchowski limit" of around 10^8 M^-1.s^-1, and when the 
same protein-protein interaction is measured in buffer containing ~250 mM 
NaCl, the rate falls to ~10^8 M^-1.s^-1, somewhere close to the 
"Smoluchowski limit".
So any assumption about the association rate constant could easily be out 
by a factor of 10^4, which in turn gives you a 10^4 error in calculating 
the koff from the Kd!
Steve Halford
----------------------
Professor Stephen E. Halford FRS
Department of Biochemistry,
School Of Medical Sciences,
University of Bristol,
University Walk,
Bristol BS8 1TD, UK.
tel: +44-(0)117-331-2156 - NB, new phone and new FAX number
FAX: +44-(0)117-331-2168
E-mail: s.halford at bristol.ac.uk

--On 07 April 2008 08:20 -0400 Allen Minton <minton at helix.nih.gov> wrote:

> If memory serves, many if not most protein association reactions have
> very similar bimolecular association rate constants (say within a factor
> of 3 or so).  I seem to remember something on the order of 10^5 mol^-1
> sec^-1, but I'm not sure of that, you'd better look it up.  (Note: this
> is orders of magnitude smaller than the upper limit calculated according
> to Smoluchowski, which does not take into account the orientational
> constraints applying to a specific association that greatly increase the
> entropic barrier to complex formation.)  Therefore, given the equilibrium
> dissociation constant you should be able to estimate the dissociation
> rate constant to within this level of uncertainty.
>
> Diffusion coefficients are irrelevant.
>
> Allen Minton
>
>
> At 07:59 PM 4/5/2008, Wenta Nikola wrote:
>
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> Dear Colleagues!
> In order to make my question more precise, I want to to calculate the
> theoretically diffusion-controlled maximum possible k_off rate of a given
> dimer based it's kD (from SE run), in combination with a calculated
> diffusion coefficient for monomer and dimer by HydroPro.
> If anyone had any suggestions how to calculate that k_off rate, I would
> be very grateful.
> Niko
>
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