Equivalent amino acids for similarity searches

Peter Gegenheimer peterg at rnaworld.bio.ukans.edu
Thu Mar 24 00:58:47 EST 1994

>In article <2mmfdp$t1n at usenet.INS.CWRU.Edu>, dy684 at cleveland.Freenet.Edu
>(Roberto Albinoni) wrote:
> .....
>> i wonder if someone to point me to appropriate references on which amino
>> acids can be considered most similar based on their chemistry and function,
>> and also how one can 'score' the similarity of two proteins based not only
>> on identical residues, but also on amino acids which belong to the same
>> chemical families.

One point to consider: the amino acid substitutions which are ALLOWED BY NATURE 
during evolution are NOT necessarily the same as those which preserve the "chemical 
similarity" of the side-chain. A number of follow-up postings have called attention 
to the various evolutionary substitution matrices available. I should like to add two 
further helpful items of information.

1) If you are working with one member of a family of (highly-conserved) proteins, 
and you have their amino acid sequences aligned in a way you KNOW to be correct 
(i.e., all residues in one column had the same evolutionary ancestor), then the
OBSERVED variation at each position is a good clue to the ALLOWED variation at that 

2) The best work on amino acid substitutions from a combined chemical and 
evolutionary angle is that of D. Bordo and P. Argos, Suggestions for "safe" residue 
substitutions in site-directed mutagenesis, J. Mol. Biol. 217, 721-729 (1991). This
work examines nine conserved "families" of proteins all of whose 3-D crystal 
structures are known, and tabulates the allowed substitutions for amino acids in the
same 3-D environment.

These substitutions are generally in accord with our mutagenesis experience.
Hope this helps.

|  Peter Gegenheimer                          |  pgegen at kuhub.cc.ukans.edu      |
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