Protein Structure and Function: Application of Bioinformatics Methods - John Rigden 2014

Protein Function Prediction Based on Surface Properties
Function Prediction from Surface Properties
Electrostatic Surface

Enzyme active sites are frequently characterized by a region of high electrostatic potential, which can be viewed as a trade-off between the biological function of the protein and its stability (Beadle and Shoichet 2002). Consequently, mapping surface electrostatic potential can sometimes be useful for predicting functional sites that may serve as active centres (Elcock 2001) or DNA- and RNA-binding sites (Tsuchiya et al. 2005). For example, using the PatchFinderPlus program, the largest patch with a positive electrostatic potential is displayed on the protein surface (Fig. 7.2), which often corresponds to the binding site of Proteins interacting with Nucleic Acids (Stawiski et al. 2003).

Below are Examples where functional conservation is driven by Structure/111.html">Surface Conservation rather than protein fold conservation or conserved residues. The best-known example is the catalytic triad of Serine proteases, where even the three key Amino Acids of the Active Site (typically His, Asp, and Ser) can vary. The only invariant feature is The surface of the active site and the electrostatic nature of its catalytic activity. Consequently, comparing the molecular surfaces of unknown proteins against Databases of similarly defined surfaces proves to be highly valuable.

For instance, eF-Site (Kinoshita and Nakamura 2003) searches a database of protein surfaces described in terms of their electrostatic and hydrophobic properties. A query regarding the protein of interest can be submitted to the most appropriate database (such as Antibodies, active sites, phosphate-binding sites, or a database derived from PROSITE Definitions), returning a set of proteins that share similar Surface Properties with the query protein.

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Fig. 7.2. Prediction of functional sites using PatchFinderPlus. Shown is the crystallographic STRUCTURE OF THE BglI restriction endonuclease (protein atoms rendered as Van der Waals spheres) complexed with its specific DNA sequence (Newman et al. 1998). The largest patch of positive electrostatic potential is highlighted in dark grey.