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A structural study for the optimisation of functional motifs encoded in protein sequences
Allegra Via1, Manuela Helmer-Citterich
1Centre for Molecular Bioinformatics, Dept, of Biology, University of Rome Tor Vergata, Rome, Italy. allegra@cbm.bio.uniroma2.it
BMC Bioinformatics
|May 4, 2004
Summary
This study introduces a new method to improve protein pattern accuracy by incorporating structurally conserved residues. This enhances pattern selectivity and sensitivity, aiding in the identification of functionally important residues.
Area of Science:
- Bioinformatics
- Structural Biology
- Computational Biology
Background:
- PROSITE patterns often exhibit low sensitivity and specificity, missing true positives or including false positives.
- This inaccuracy can stem from key functional or structural residues not being represented in standard sequence patterns.
- Multiple sequence alignments, commonly used for pattern construction, may fail to align structurally conserved residues, leading to their omission.
Purpose of the Study:
- To develop and present a novel procedure for enhancing the sensitivity and/or specificity of underperforming protein sequence patterns.
- To improve the accuracy of functional motif identification in protein families.
- To identify functionally and structurally important residues missed by existing patterns.
Main Methods:
- Identification of structurally conserved residues in true positive protein structures using computational techniques and visual inspection.
- Extension of existing sequence patterns by incorporating the positions of identified structurally conserved residues that fall outside the original pattern.
- Optimization of these extended patterns for sensitivity and specificity against the SWISS-PROT database.
Main Results:
- Application of the method to eight PROSITE patterns demonstrated improved pattern selectivity.
- In seven out of eight cases, incorporating information from structural analysis enhanced pattern selectivity and, in some instances, both selectivity and sensitivity.
- The procedure successfully identified functionally significant residues, providing insights into their biological roles.
Conclusions:
- The developed method is applicable to any functional motif or pattern beyond PROSITE, provided at least two true positive structures are available.
- The computational tool for identifying structurally conserved residues is available upon request and will be accessible via a web server.
- This procedure is designed for pattern database curators and researchers studying specific protein families lacking selective patterns.