Mark Cohen said:
> >- "mutation matrices ... differ, depending on whether they were derived
> > from protein pairs that are distantly homologous or from protein pairs
> > that are closely homologous". What a discovery !!
> >- how can anyone align confidently protein sequences that are "distantly
> > homologous" and use the results to build a matrix ?
> We did not align "distantly homologous" and build a matrix from the results
> We aligned all the proteins in the data base with all the others.
> [...]
OK, but the question still stands, how does one confidently align
those segments that are "distantly homologous" (your term)?
> Where the scores obtained (using Dayhoff's 1978 matrix) indicated
> that the alignments were significant (ie that the probability of the
> alignment was significantly higher than alignment of two random
> sequences) these alignments were used in the construction of the matrix.
So, then, "distant" means "significant"?
> >- what are "distantly homologous" proteins ? [...]
> [Tautology deleted] Proteins for which the alignment score is high
> enough above the score of aligned random sequences yet not so high
> as to be unambiguously related.
If only that had been stated in the paper...
> >- what is the influence of the enormous redundancy found in protein
> > databanks (hundreds of cytochromes, thousands of histones, zillions of
> > globulins, ...)
> We will in future publish the matrices calculated with, without and only for
> the immunoglobulins. The results do not change our opinion significantly.
Ditto. Just the single sentence would have helped.
> >- the explanation for the -3/2 power concerning the probability of
> > a gap is a joke ?
> The k^-3/2 term is an experimental result. The probability of the
> two ends of a chain being close in space is dependant on the length
> of the chain as described in the paper, or you can read Flory's book
> on polymers.
I can't say where I heard this (perhaps they will post) but others
have found this result also.
> > Well, I prefer to stop here. May I draw your attention on the paper
> >by Jones, Taylor and Thornton in the last CABIOS issue ? Their aim was also
> >to build an updated Dayhoff matrix. They did it, with the difference that
> >their procedure is crystal clear. And that, by necessity, their matrix was
> >not built with "distantly homologous proteins".
> Jones et al found like us that the differences between the Dayhoff
> 1978 matrix and the recalculated matrix were largest for the least
> common amino acid pairs, eg W-Y or W-C etc. Their paper is somewhat
> longer than ours hence their more detailed explanation.
I don't think so, I think it was just a matter of presention. Just a
few sentences in Dr. Cohen's post have cleared a number of
misunderstandings up.
dan
--
dr. dan davison/dept. of biochemical and biophysical sciences/univ. of
Houston/4800 Calhoun/Houston,TX 77204-5934/davison at uh.edu/DAVISON at UHOU
-----RIP Isaac Asimov 1920-1992 I'll miss him --------------------
Disclaimer: As always, I speak only for myself, and, usually, only to
myself.
