on- and off-rate of antibodies

Dima Klenchin klenchin at facstaff.REMOVE_TO_REPLY.wisc.edu
Thu Feb 3 13:19:30 EST 2000


ChenHA <hzhen at freeuk.com> 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.  

I am no expert in this field so I did not know it. Is this really true? 
What distances are we talking about? 

: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.  

_Very_ simplistic - and I perfectly realize that. This geometrical 
correction is pure formalism, in which, upon calculations, all other 
contributing factors are included. Much like the Stokes radius. 
Makes a lot of sense mainly because we usually have no idea 
about relative contribution of all the possible factors. 

:Many interactions would lie in a limited
: range (~ 10^5-10^6
:M-1 s-1 I think), 

Yes, my point was exactly this. On rates of probably >90% of all 
bilogical interactions will be within a single order of magnitude. 

:but some have on-rate which is close to the diffusion limit
: (~10^9) 

That's for ions. Drop it one order for proteins.

: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.
:
Wow! I did not know such thing exist! Really? How come? Do they 
behave like strong magnets or what? 

        - Dima




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