Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jul;38(Web Server issue):W402-6.
doi: 10.1093/nar/gkq323. Epub 2010 May 5.

HotPoint: hot spot prediction server for protein interfaces

Nurcan Tuncbag  1 , Ozlem Keskin, Attila Gursoy
Affiliations

HotPoint: hot spot prediction server for protein interfaces

Nurcan Tuncbag et al. Nucleic Acids Res. 2010 Jul.

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.

PubMed Disclaimer

Figures

Figure 1.
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.
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.
See this image and copyright information in PMC

References

    1. Bogan AA, Thorn KS. Anatomy of hot spots in protein interfaces. J. Mol. Biol. 1998;280:1–9. - PubMed
    1. Clackson T, Wells JA. A hot spot of binding energy in a hormone-receptor interface. Science. 1995;267:383–386. - PubMed
    1. Wells JA. Systematic mutational analyses of protein-protein interfaces. Meth. Enzymol. 1991;202:390–411. - PubMed
    1. Keskin O, Ma B, Nussinov R. Hot regions in protein–protein interactions: the organization and contribution of structurally conserved hot spot residues. J. Mol. Biol. 2005;345:1281–1294. - PubMed
    1. Keskin O, Gursoy A, Ma B, Nussinov R. Principles of protein–protein interactions: what are the preferred ways for proteins to interact? Chem. Rev. 2008;108:1225–1244. - PubMed

Publication types