WebFEATURE: An interactive web tool for identifying and visualizing functional sites on macromolecular structures

Abstract

WebFEATURE (http://feature.stanford.edu/webfeature/) is a web-accessible structural analysis tool that allows users to scan query structures for functional sites in both proteins and nucleic acids. WebFEATURE is the public interface to the scanning algorithm of the FEATURE package, a supervised learning algorithm for creating and identifying 3D, physicochemical motifs in molecular structures. Given an input structure or Protein Data Bank identifier (PDB ID), and a statistical model of a functional site, WebFEATURE will return rank-scored 'hits' in 3D space that identify regions in the structure where similar distributions of physicochemical properties occur relative to the site model. Users can visualize and interactively manipulate scored hits and the query structure in web browsers that support the Chime plug-in. Alternatively, results can be downloaded and visualized through other freely available molecular modeling tools, like RasMol, PyMOL and Chimera. A major application of WebFEATURE is in rapid annotation of function to structures in the context of structural genomics.

Figure 1

The WebFEATURE interface allows the user to choose a structure to scan by either entering a PDB ID or uploading a structure from the local computer. The user also chooses a site model to use for scanning from the pull-down menu and has the option of receiving email notification of results. The user can retrieve more information on the selected model by clicking the info button.

Figure 2

The output of a WebFEATURE scan for an ATP binding site in Casein Kinase-1 (PDB ID: 1csn) shows the hits, above cutoff, superimposed on the structure and crystallographically bound ATP. Hit score statistics are plotted in a histogram to the right of the Chime viewer. By entering a new cutoff in the Cutoff text field, or by clicking on the histogram, the user can change the displayed hits by score. Buttons are provided to change the representation of the molecule and hits. Details on the statistical model are also provided.

Figure 3

WebFEATURE provides a 2D plot of the statistical model for each available functional site. In this model for ATP binding, each cell represents the significance of a property in a radial volume around the functional site. Properties that are significantly present in the sites versus the non-sites are marked in green and those that are significantly absent are marked in red.