on- and off-rate of antibodies
hzhen at freeuk.com
Wed Feb 2 20:34:36 EST 2000
Dima Klenchin wrote:
> ON rate for all biological reactions is, in first and very good approxymation,
> a frequency of diffusional collision corrected by the geometrical factor (molecules
> have to hit each other with "correct" sides which contain recognition sites).
> Imagine diffusiing spheres with pieces of Velcro attached to their sides -
> non-Velcro covered surfaces do not interact, covered do. There isn'ts much
> you can do to increase the frequency of them sticking to each other - you can't
> increase diffusional coefficients and you cannot increase the surface covered
> with Velcro (because both are _given_ by design; unless you introduce some
> misterious long range forces).
This is not so mysterious. The long-range electrostatic steering has been the subject of
many papers by Alan Fersht and others. The analogy you used is an excellent one, although
slightly simplistic because it assume that the on-rate is only determined by the diffusion
and geometric consideration, in which case you would expect on-rates for all interaction to
be the same. They are not of course, this may be due to a number of factors such as size,
electrostatic interactions, etc. Many interactions would lie in a limited range (~ 10^5-10^6
M-1 s-1 I think), but some have on-rate which is close to the diffusion limit (~10^9) and
this is due to this 'mysterious force' you mentioned. A few have on-rates which exceed the
diffusion limit (such as the lac operator-lac repressor protein-DNA interaction) which may be
due to electrostatic interactions or other unusual mechanisms.
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