From: Tom Laue <Tom.Laue@unh.edu>
  To  : Borries Demeler <demeler@bioc09.v19.uthscsa.edu>
  Date: Wed, 26 Apr 2000 13:49:34 -0400

Re: NONLIN question

Hi Bo-
Sticking with a mixture of monomers and dimers:
Any situation in which the concentration of dimers is not strictly
proportional to the square of the concentration of monomers will give rise
to LnK2 varying from channel to channel. The case you point out,
incompetent monomer, is one situation. I've found that the more common case
is irreverible dimer (or aggregate). Another case is if there is
thermodynamic nonideality in addition to association. 

The cause of the better fit when separate LnKs are used can be diagnosed by
noting if there is a systematic change in LnK2 with rotor speed and loading
concentration.  Case 1- If LnK2 decreases with increasing rotor speed and
decreases with increasing concentration, then you have some irreversible
aggregate.
 Case 2- If LnK2 is relatively constant with rotor speed (for a given
loading concentration), but decreases with increasing loading
concentration, you have nonideality or incompetent monomer.
Nature, of course, doesn't care, and will give both cases simultaneously.

Importantly, if the confidence intervals of LnK2 overlap as a function of
rotor speed and loading concentration, you have thermodynamic proof of a
reversible association with the stoichiometry of 2. 
Best wisehs,
Tom



At 11:09 AM 4/26/2000 -0500, you wrote:
>Dear RASMB'ers,
>
>I have a question that keeps popping up - I never really thought about it
>much, but maybe someone has already:
>
>Sometimes, when fitting a monomer-dimer fit for example, one can obtain a 
>substantially better variance by turning on the multi-channel option for 
>LnK2 in Nonlin. I suppose one possible interpretation for this would be
>the presence of a portion of the sample being in incompetent monomer state
>the rest can reversibly associate like a normal M/D system.
>
>What other possible interpretations exist for this symptom? And what 
>models have people used to fit that? 
>
>I suppose for the case of an incompetent monomer an additional exponential
>term with the monomer MW and an amplitude proportional to the fraction of the
>incpt. monomer would work, where the fraction of the total concentration
>would be an adjustable (floating) parameter. Seems like something quite
>sensitive to cross-correlation.
>
>Anyway, if you have dealt with such a system previously, I'd be interested 
>to hear from you.
>
>Thanks in advance for any comments and suggestions, -Borries
>
--------------------------------------------
Tom Laue
Professor and Director of CAMIS
University of New Hampshire
Biochemistry and Molecular Biology
Rudman-379
46 College Rd.
Durham, NH 03824-3544

Phone: 603-862-2459
FAX:   603-862-4013
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