A novel statistical ligand-binding site predictor: application to ATP-binding sites.

Structural genomics initiatives are leading to rapid growth in newly determined protein 3D structures, the functional characterization of which may still be inadequate. As an attempt to provide insights into the possible roles of the emerging proteins whose structures are available and/or to complement biochemical research, a variety of computational methods have been developed for the screening and prediction of ligand-binding sites in raw structural data, including statistical pattern classification techniques. In this paper, we report a novel statistical descriptor (the Oriented Shell Model) for protein ligand-binding sites, which utilizes the distance and angular position distribution of various structural and physicochemical features present in immediate proximity to the center of a binding site. Using the support vector machine (SVM) as the classifier, our model identified 69% of the ATP-binding sites in whole-protein scanning tests and in eukaryotic proteins the accuracy is particularly high. We propose that this feature extraction and machine learning procedure can screen out ligand-binding-capable protein candidates and can yield valuable biochemical information for individual proteins.