title: Multiresolution analysis uncovers hidden conservation of properties in structurally and functionally similar proteins.
abstract: Physicochemcial properties of amino acids are important factors in determining protein structure and function. Most approaches make use of averaged properties over entire domains or even proteins to analyze their structure or function. This level of coarseness tends to hide the richness of the variability in the different properties across functional domains. This paper studies the conservation of physicochemical properties in a functionally similar family of proteins using a novel wavelet-based technique known as multiresolution analysis. Such an analysis can help uncover characteristics that can otherwise remain hidden. We have studied the protein kinase family of sequences and our findings are as follows: (a) a number of different properties are conserved over the functional catalytic domain irrespective of the sequence identities; (b) conservation of properties can be observed at different frequency levels and they agree well with the known structural/functional properties of the subdomains for the protein kinase family; (c) structural differences between the different kinase family members are reflected in the waveforms; and (d) functionally important mutations show distortions in the waveforms of conserved properties. The potential usefulness of the above findings in identifying functionally similar sequences in the twilight and midnight zones is demonstrated through a simple prediction model for the protein kinase family which achieved a recall of 93.7% and a precision of 96.75% in cross-validation tests.
authors.affiliation: Bioinformatics Institute, 30, Biopolis Street, #07-01, Matrix, Singapore.
authors.forename: Gek-Huey
authors.initials: GH
authors.lastname: Chua
authors.forename: Arun
authors.initials: A
authors.lastname: Krishnan
authors.forename: Kuo-Bin
authors.initials: KB
authors.lastname: Li
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002384:Catalysis; D017124:Conserved Sequence; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry* / Q000145:classification; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D011494:Protein Kinases