Predicting and annotating catalytic residues: An information theoretic approach

Beckett Sterner, Rohit Singh, Bonnie Berger

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


We introduce a computational method to predict and annotate the catalytic residues of a protein using only its sequence information, so that we describe both the residues' sequence locations (prediction) and their specific biochemical roles in the catalyzed reaction (annotation). While knowing the chemistry of an enzyme's catalytic residues is essential to understanding its function, the challenges of prediction and annotation have remained difficult, especially when only the enzyme's sequence and no homologous structures are available. Our sequence-based approach follows the guiding principle that catalytic residues performing the same biochemical function should have similar chemical environments; it detects specific conservation patterns near in sequence to known catalytic residues and accordingly constrains what combination of amino acids can be present near a predicted catalytic residue. We associate with each catalytic residue a short sequence profile and define a Kullback-Leibler (KL) distance measure between these profiles, which, as we show, effectively captures even subtle biochemical variations. We apply the method to the class of glycohydrolase enzymes. This class includes proteins from 96 families with very different sequences and folds, many of which perform important functions. In a cross-validation test, our approach correctly predicts the location of the enzymes' catalytic residues with a sensitivity of 80% at a specificity of 99.4%, and in a separate cross-validation we also correctly annotate the biochemical role of 80% of the catalytic residues. Our results compare favorably to existing methods. Moreover, our method is more broadly applicable because it relies on sequence and not structure information; it may, furthermore, be used in conjunction with structure-based methods.

Original languageEnglish (US)
Pages (from-to)1058-1073
Number of pages16
JournalJournal of Computational Biology
Issue number8
StatePublished - Oct 1 2007
Externally publishedYes


  • Algorithms
  • Computational molecular biology
  • Information theory
  • Multiple sequence alignment
  • Protein folding

ASJC Scopus subject areas

  • Modeling and Simulation
  • Molecular Biology
  • Genetics
  • Computational Mathematics
  • Computational Theory and Mathematics


Dive into the research topics of 'Predicting and annotating catalytic residues: An information theoretic approach'. Together they form a unique fingerprint.

Cite this