title: InCa-SiteFinder: a method for structure-based prediction of inositol and carbohydrate binding sites on proteins.
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%.
authors.affiliation: Institute of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kulharia
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Bridgett
authors.forename: Roger S
authors.initials: RS
authors.lastname: Goody
authors.forename: Richard M
authors.initials: RM
authors.lastname: Jackson
mesh_terms: D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods*; D007294:Inositol / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002241:Carbohydrates; D011506:Proteins; D007294:Inositol