Structure-based amino acid substitution matrices have been developped. I
know some articles that describe such matrices (there may be others):
Overington J., Johnson M.S., Sali A. & Blundell T.L. (1990) Tertiary structural
constraints on protein evolutionary diversity: templates, key residues and structure
prediction. Proc. R. Soc. Lond. B 241:132-145
Overington J., Donnelly D., Johnson M.S., Sali A. & Blundell T.L. (1992)
Environment-specific amino acid substitution tables: Tertiary templates and
prediction of protein folds. Prot. Sci. 1:216-226
Risler J.L., Delorme M.O., Delacroix H. & Henaut A. (1988) Amino acid substitutions
in structurally related proteins a pattern recognition approach.
J. Mol. Biol. 204:1019-1029
Hope this helps,
Laurent Duret duret at biomserv.univ-lyon1.fr
Tel: +33 22.214.171.124 Fax: +33 126.96.36.199
Laboratoire de Biometrie, Genetique et Biologie des Populations
Bat 741 - URA CNRS 243 Universite Claude Bernard - Lyon I
43, Bd du 11 Novembre 1918
69622 Villeurbanne cedex FRANCE
In article 38556 at ac.dal.ca, aroger at ac.dal.ca writes:
>I'm interested in improving empirically-based amino acid
>substitution model for use in phylogenetic analysis.
>>One method which may improve upon existing models (like
>the Dayhoff models which programs like PROTDIST and
>PROTML use) is to determine whether the propensity
>of an amino acid (say X) to change to another amino acid
>(Y) depends upon the structural context in which it is
>found. For instance, it may be the case that the
>transition X<-->Y is very frequent in a secondary
>structural element like an alpha helix, but is very
>rare in a beta-sheet or a beta-turn. Similarly
>a hydrophobic amino acid (lets call it Z) may
>frequently change to another hydrophobic amino acid (say Q (
>keep in mind that I'm not using the one-letter amino acid code))
>in a core region of a protein while the change to a charged
>or "hydrophilic" amino acid in this region may be very rare.
>The dynamics of change are likely going to be very different
>on a solvent accessible region of a protein.
>Thus it is possible that "averaged" substitution models
>like that of Dayhoff, may be very poor approximations of
>the actual site by site frequencies simply because they
>are averages of many dissimilar models.
>>If what I say is possibly true, it should be of interest
>to develop structure-based amino acid substitution matrices
>for a whole variety of proteins for which one of the homologues
>has been crystallized (making the assumption that the structures
>have not changed too much). Doing this may allow us to develop
>general substitution matrices for structural elements and to
>test whether the different matrices are significantly
>different from one another (this may in turn help those
>interested in protein engineering) and in what way.
>The application of these models to protein phylogeny would
>only require the user, to provide structural information in addition
>to an alignment.
>>Is someone already doing this? Does anyone know of references
>to any such investigation?
>>I'd be interested to hear what those involved in development of
>phylogenetic methods have to say about this idea
>Dept. of Biochemistry
>aroger at ac.dal.ca