From: JOHN PHILO <JOHN.PHILO@amgen.com>
  To  : Jim Cole <jim_cole@merck.com>
  Date: 3 Nov 1995 08:31:39 U

Re: Nonideality

Jim,

I agree with Jack Correia that "incompetent monomer" might easily
make it appear that there is a large non-ideality.  You haven't 
really indicated whether adding this large non-ideality term gives a 
good fit of the data.  That is, is your concern only the magnitude 
of the non-ideality, or are your doubts based in part on the fact 
that this model still doesn't fully explain the data?

Also, to add to Jack's point about incompetent monomer, you 
might also have the situation where there is a heterogeneity of 
association constants (i.e. none of the material may be totally 
incompetent to dimerize, but some may dimerize poorly).  I 
assume your protein at least appears homogenous on SDS gels, 
but there could be post-translational modifications that would 
alter the association constants but would not give obvious 
heterogeneity on an SDS gel (e.g. some variable processing 
at the amino or carboxy terminus that leads to differences of 
1 or 2 amino acids, or perhaps covalent modifications such as 
deamidation or even phosphorylation).  Is this protein 
homogeneous by isoelectric focusing and mass spectroscopy?

Regards,

John Philo, Amgen