Re and Re: Gaps and PAMs

Mon Jun 29 13:02:00 EST 1992

In reply to Sean Eddy's posting: there is a set of proteins whose sequences
are rather different (I dare not write "remotely similar", which looks
rather strange...) but which can be aligned on the basis of 3-D
structures in the family. It is the aminoacyl-tRNA synthetases.
1) an alignment of the 10 class I aaRS from E. coli, based on three
   crystal structures, should be published soon (I hope) by Landes et al.
   in J. Mol. Biol. (if God permits. The paper is submitted).
2) as expected, NO pairwise alignment performed with GAP or BESTFIT is
   totally consistent with the "3-D alignment".
3) we have made a thorough study of the ability of different scoring
   indices to produce a correct *classification* (not phylogeny) of the
   globins and the synthetases. As expected (again) the BESTFIT and FASTA
   scores failed to classify correctly the vertebrate globins and the aaRS.
   The classifications are much more satisfactory when the Z-scores are
   taken as distance indices. This will appear soon in NAR.
4) the conclusion is clear: alignment scores can in no way be used to
   compare different alignments, except when the sequences are very close
   to one another. This is not a great surprise.
5) may I humbly direct you to a paper that I published some time ago (J.
   Mol. Biol. (1988) 204, 1019-1029) where I tried to build a scoring
   matrix based on 3-D superpositions ?
To come back to the SCIENCE paper: does all this stuff mean that papers
which need experimental details should not be published in Science ?
J-L. Risler   Centre de Genetique Moleculaire   risler at frcgm51.bitnet
                Gif sur Yvette  France          bionet at frcgm51.bitnet

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