ResBoost: characterizing and predicting catalytic residues in enzymes

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Creator
  • Alterovitz, Ron
    • Affiliation: College of Arts and Sciences, Department of Computer Science
  • Arvey, Aaron
    • Other Affiliation: Department of Computer Science and Engineering, University of California, San Diego, USA
  • Sankararaman, Sriram
    • Other Affiliation: Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, USA
  • Dallett, Carolina
    • Other Affiliation: Department of Bioengineering, University of California, Berkeley, USA
  • Freund, Yoav
    • Other Affiliation: Department of Computer Science and Engineering, University of California, San Diego, USA
  • Sjölander, Kimmen
    • Other Affiliation: Department of Bioengineering, University of California, Berkeley, USA
Abstract
  • Abstract Background Identifying the catalytic residues in enzymes can aid in understanding the molecular basis of an enzyme's function and has significant implications for designing new drugs, identifying genetic disorders, and engineering proteins with novel functions. Since experimentally determining catalytic sites is expensive, better computational methods for identifying catalytic residues are needed. Results We propose ResBoost, a new computational method to learn characteristics of catalytic residues. The method effectively selects and combines rules of thumb into a simple, easily interpretable logical expression that can be used for prediction. We formally define the rules of thumb that are often used to narrow the list of candidate residues, including residue evolutionary conservation, 3D clustering, solvent accessibility, and hydrophilicity. ResBoost builds on two methods from machine learning, the AdaBoost algorithm and Alternating Decision Trees, and provides precise control over the inherent trade-off between sensitivity and specificity. We evaluated ResBoost using cross-validation on a dataset of 100 enzymes from the hand-curated Catalytic Site Atlas (CSA). Conclusion ResBoost achieved 85% sensitivity for a 9.8% false positive rate and 73% sensitivity for a 5.7% false positive rate. ResBoost reduces the number of false positives by up to 56% compared to the use of evolutionary conservation scoring alone. We also illustrate the ability of ResBoost to identify recently validated catalytic residues not listed in the CSA.
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Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Ron Alterovitz et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Bioinformatics
Journal volume
  • 10
Journal issue
  • 1
Page start
  • 197
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2105
Bibliographic citation
  • BMC Bioinformatics. 2009 Jun 27;10(1):197
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • August 23, 2012

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file details 1471-2105-10-197.pdf 2019-05-07 Public Download
file details 1471-2105-10-197.xml 2019-05-07 Public Download
file details ResBoost dataset. Details on the enzymes in the ResBoost dataset and additional base classifiers. 2019-05-07 Public Download