Wu, T. D. and Brutlag, D. L. (1996). Discovering Empirically Conserved Amino Acid Substitution Groups in Databases of Protein Families. ISMB-96, 3, 230-240.
Department of
Biochemistry, Stanford
University School of Medicine, Stanford
California 94305-5307.
This paper introduces a method for identifying amino acid
substitution groups that are conserved empirically in aligned
positions from databases of protein families. Existing approaches
view amino acid substitution as a pairwise phenomenon and
characterizes it using substitution matrices. In contrast, the method
presented here identifies subsets of amino acids that are conserved
empirically using a conditional distribution matrix, which contains
entries for every combination of individual amino acids and subsets
of amino acids. Each row in the conditional distribution matrix
contains the distribution of amino acids in those aligned positions
that contain a given subset of amino acids. The algorithm converts a
database of protein families into a conditional distribution matrix
and then examines each possible substitution group for evidence of
conservation. A substitution group is empirically conserved when it
has characteristics of compactness and isolation, meaning that amino
acids within the group substitute for one another at a higher
frequency than amino acids outside the group. The algorithm is
applied to the blocks and hssp databases. Twenty amino acid
substitution groups are found to be conserved empirically in both
databases. These groups provide insight into biochemical properties
that are conserved in protein evolution.
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