Predicting kinase substrates using conservation of local motif density

Bioinformatics. 2012 Apr 1;28(7):962-9. doi: 10.1093/bioinformatics/bts060. Epub 2012 Feb 1.

Abstract

Motivation: Protein kinases represent critical links in cell signaling. A central problem in computational biology is to systematically identify their substrates.

Results: This study introduces a new method to predict kinase substrates by extracting evolutionary information from multiple sequence alignments in a manner that is tolerant to degenerate motif positioning. Given a known consensus, the new method (ConDens) compares the observed density of matches to a null model of evolution and does not require labeled training data. We confirmed that ConDens has improved performance compared with several existing methods in the field. Further, we show that it is generalizable and can predict interesting substrates for several important eukaryotic kinases where training data is not available.

Availability and implementation: ConDens can be found at http://www.moseslab.csb.utoronto.ca/andyl/.

Contact: alan.moses@utoronto.ca

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • CDC28 Protein Kinase, S cerevisiae / chemistry
  • Computational Biology / methods*
  • Conserved Sequence
  • Models, Statistical
  • Phosphorylation
  • Phosphotransferases / chemistry*
  • Protein Interaction Domains and Motifs*
  • Sequence Alignment*
  • Substrate Specificity

Substances

  • Phosphotransferases
  • CDC28 Protein Kinase, S cerevisiae