eF-seek: prediction of the functional sites of proteins by searching for similar electrostatic potential and molecular surface shape

Abstract

We have developed a method to predict ligand-binding sites in a new protein structure by searching for similar binding sites in the Protein Data Bank (PDB). The similarities are measured according to the shapes of the molecular surfaces and their electrostatic potentials. A new web server, eF-seek, provides an interface to our search method. It simply requires a coordinate file in the PDB format, and generates a prediction result as a virtual complex structure, with the putative ligands in a PDB format file as the output. In addition, the predicted interacting interface is displayed to facilitate the examination of the virtual complex structure on our own applet viewer with the web browser (URL: http://eF-site.hgc.jp/eF-seek).

Figure 1.

An example of a result page. In the result page, a density plot of the search result and a text box are shown, as described in the main text. In this example, c-AMP- dependent protein kinase (PDB: 1atp chain E) was used as a query, and the name of the top hit, which corresponds to the filled circle in the top right corner, is shown in the text box. The scale of the density plot is shown according to the color bar on the right side of the plot.

Figure 2.

An example of a view structure page. In the view structure page, interactive view of the putative complex is provided with two jV [15] panels. The complex structure with ribbon model (left panel) and that with the surface model (right panel) are presented. In the right panel, the residues within 5.0 Å from the putative ligand are specified with ball and stick model. These viewers can be rotated and translated with the mouse operation synchronously. In this example, the binding mode of ADP with the query protein (PDB: 1atp, E chain), predicted from the binding site appearing in 1l3r in PDB (c-AMP-dependent protein kinase), is shown.