InCa-SiteFinder: a method for structure-based prediction of inositol and carbohydrate binding sites on proteins

Mahesh Kulharia, Stephen J Bridgett, Roger S Goody, Richard M Jackson

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Carbohydrate binding sites are considered important for cellular recognition and adhesion and are important targets for drug design. In this paper we present a new method called InCa-SiteFinder for predicting non-covalent inositol and carbohydrate binding sites on the surface of protein structures. It uses the van der Waals energy of a protein-probe interaction and amino acid propensities to locate and predict carbohydrate binding sites. The protein surface is searched for continuous volume envelopes that correspond to a favorable protein-probe interaction. These volumes are subsequently analyzed to demarcate regions of high cumulative propensity for binding a carbohydrate moiety based on calculated amino acid propensity scores. InCa-SiteFinder(1) was tested on an independent test set of 80 protein-ligand complexes. It efficiently identifies carbohydrate binding sites with high specificity and sensitivity. It was also tested on a second test set of 80 protein-ligand complexes containing 40 known carbohydrate binders (having 40 carbohydrate binding sites) and 40 known drug-like compound binders (having 58 known drug-like compound binding sites) for the prediction of the location of the carbohydrate binding sites and to distinguish these from the drug-like compound binding sites. At 73% sensitivity the method showed 98% specificity. Almost all of the carbohydrate and drug-like compound binding sites were correctly identified with an overall error rate of 12%.

Original languageEnglish
Pages (from-to)297-303
Number of pages7
JournalJournal of Molecular Graphics and Modelling
Volume28
Issue number3
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Binding Sites
  • Carbohydrates/chemistry
  • Computational Biology/methods
  • Inositol/chemistry
  • Protein Binding
  • Protein Conformation
  • Proteins/chemistry

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