HotPoint: hot spot prediction server for protein interfaces

Abstract

The energy distribution along the protein-protein interface is not homogenous; certain residues contribute more to the binding free energy, called 'hot spots'. Here, we present a web server, HotPoint, which predicts hot spots in protein interfaces using an empirical model. The empirical model incorporates a few simple rules consisting of occlusion from solvent and total knowledge-based pair potentials of residues. The prediction model is computationally efficient and achieves high accuracy of 70%. The input to the HotPoint server is a protein complex and two chain identifiers that form an interface. The server provides the hot spot prediction results, a table of residue properties and an interactive 3D visualization of the complex with hot spots highlighted. Results are also downloadable as text files. This web server can be used for analysis of any protein-protein interface which can be utilized by researchers working on binding sites characterization and rational design of small molecules for protein interactions. HotPoint is accessible at http://prism.ccbb.ku.edu.tr/hotpoint.

Figure 1.

The output page of HotPoint for the p53 DNA binding domain/53BP2 protein complex (pdb:1ycs, chain A and B). Interface residues of this complex are shown in the table with hot spot predictions: (1) the coordinates of interface residues can be downloaded; (2) hot spot prediction results are also downloadable; and (3) interface with predicted hot spots can be visualized by JMol.

Figure 2.

IL-2/IL-2 receptor complex. The PDB code for this complex is 1z92. The red-colored residues are correctly predicted hot spots. The blue-colored ones are correctly predicted non-hot spots. The yellow-colored residues represent non-hot spot residues that are incorrectly predicted as hot spots.