From Protein Structure to Function with Bioinformatics.pdf

7 Predicting Protein Function from Surface Properties 1817.5.2 Hot-Spot Regions in Protein InterfacesIt has been shown that certain interface residues, when mutated to alanine (in aprocess termed alanine-scanning mutagenesis), have a much greater affect on thestability of the complex than the other residues in the protein interface (Clacksonand Wells 1995). The most significant amino acids, termed “hot-spot” residues,tend to lie at the bottom of small pockets on the protein surface (Bogan and Thorn1998). The rest of the pocket is lined by residues of intermediate importance. Mostof the hot-spot residues thus defined are stored in the database ASEdb (Thorn andBogan 2001). Analysis of these residues suggests that a good hot-spot residue islarge and aromatic (tryptophan or tyrosine) or the positively charged arginine (butnot lysine). Hot-spot residues are less likely to be the smaller residues that are eitheramphiphilic (serine, theronine) or hydrophobic (valine and leucine) (Bogan andThorn 1998).Analysis of interface pockets suggests that the most significant differencebetween the pockets in the interface and those in the rest of the protein is that theinterfacial ones are more easily desolvated (Burgoyne and Jackson 2006). Thiswork used the pocket detection program Q-SiteFinder (Section 7.4.2.3, Fig. 7.6) toidentify all surface pockets. These were then ranked according to a variety of surfaceproperties. The property of pocket desolvation most reliably ranked interface pocketsFig. 7.6 The surface of the DNAse I (white, PDB code: 1ATN) in complex with actin (notshown), with all predicted Q-SiteFinder pockets (grey/black). The pockets coloured in black correspondto those occupied by atoms from actin