Janda, Jan-Oliver and Busch, Markus and Kueck, Fabian and Porfenenko, Mikhail and Merkl, Rainer (2012) CLIPS-1D: analysis of multiple sequence alignments to deduce for residue-positions a role in catalysis, ligand-binding, or protein structure. BMC BIOINFORMATICS, 13: 55. ISSN 1471-2105,
Full text not available from this repository. (Request a copy)Abstract
Background: One aim of the in silico characterization of proteins is to identify all residue-positions, which are crucial for function or structure. Several sequence-based algorithms exist, which predict functionally important sites. However, with respect to sequence information, many functionally and structurally important sites are hard to distinguish and consequently a large number of incorrectly predicted functional sites have to be expected. This is why we were interested to design a new classifier that differentiates between functionally and structurally important sites and to assess its performance on representative datasets. Results: We have implemented CLIPS-1D, which predicts a role in catalysis, ligand-binding, or protein structure for residue-positions in a mutually exclusive manner. By analyzing a multiple sequence alignment, the algorithm scores conservation as well as abundance of residues at individual sites and their local neighborhood and categorizes by means of a multiclass support vector machine. A cross-validation confirmed that residue-positions involved in catalysis were identified with state-of-the-art quality; the mean MCC-value was 0.34. For structurally important sites, prediction quality was considerably higher (mean MCC = 0.67). For ligand-binding sites, prediction quality was lower (mean MCC = 0.12), because binding sites and structurally important residue-positions share conservation and abundance values, which makes their separation difficult. We show that classification success varies for residues in a class-specific manner. This is why our algorithm computes residue-specific p-values, which allow for the statistical assessment of each individual prediction. CLIPS-1D is available as a Web service at http://www-bioinf.uni-regensburg.de/. Conclusions: CLIPS-1D is a classifier, whose prediction quality has been determined separately for catalytic sites, ligand-binding sites, and structurally important sites. It generates hypotheses about residue-positions important for a set of homologous proteins and focuses on conservation and abundance signals. Thus, the algorithm can be applied in cases where function cannot be transferred from well-characterized proteins by means of sequence comparison.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDOLE-3-GLYCEROL PHOSPHATE SYNTHASE; FUNCTIONALLY IMPORTANT RESIDUES; EXCHANGE MASS-SPECTROMETRY; STRUCTURE PREDICTION; SULFOLOBUS-SOLFATARICUS; CONSERVED RESIDUES; NUCLEIC-ACIDS; 3D STRUCTURE; SERVER; SITES; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Rainer Merkl |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 May 2020 04:55 |
| Last Modified: | 15 May 2020 04:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18898 |
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