03395nam a2200241 a 450000100080000000500110000800800410001910000160006024501510007626001800022730000190040750000200042652025020044665000190294865300200296765300280298765300140301565300260302965300270305565300270308265300270310970000170313615762922020-01-15       2009    bl uuuu     u00u1 u    #d1 aHIGA, R. H.  aEvaluating the discrimination between hot spots and the rest of surface residues based on physical and chemical properties.h[electronic resource]  aIn: INTERNATIONAL CONFERENCE OF THE BRAZILIAN ASSOCIATION FOR BIOINFORMATICS AND COMPUTATIONAL BIOLOGY, 5., 2009, Angra dos Reis. Abstracts book... Angra dos Reis: ABBCBc2009  aNão paginado.  aX-Meeting 2009.  aSince the seventies, different studies have analyzed protein structures solved in complex and publicly available in the PDB, aiming to identify physical and chemical properties distinguishing interface residues from the rest of the protein surface. The set of studied properties has also been used to predict interface residues for monomeric structures. All these studies used proteins whose structures were solved in complex such that corresponding set of interface residues were considered as known. To decide if a residue was part of the interface region, a geometric criterion was used. Usually, it was based on either the distance between residue?s heavy atoms in the interacting monomers or the variation of residue?s solvent accessible surface due to complex formation. On the other hand, it is well known that binding free energy is not evenly distributed among interface residues, with a large contribution coming from only a small subset. These binding residues, known as hot spots, are identified experimentally through a single mutation technique (alanine scanning). In this work, we tested the hypothesis that hot spots are the interface residues having the physical and chemical properties which best discriminate them from the rest of surface residues. In order to test our hypothesis, we used a previously compiled data set containing residues with structural information as well as alanine scanning results. Then, we extended them with the remaining surface residues for the corresponding structure. Discrimination between different classes of residues were measured (hot spots x non interface, non hot spots interface x non interface and interface x non interface) using a simple linear classifier. The area under ROC curve (AUC), which is insensitive to classes unbalance, was used to evaluate the discrimination. Results show that, using physical and chemical properties, hot spots are the interface residues which better discriminate from the rest of surface residues (AUC=80%). They also show that non hot spots interface residues present the lower discrimination to the rest of surface residues (AUC=63%) while interface residues (hot spots + non hot spots) present an intermediate discrimination (AUC=69%). This confirms our hypothesis and suggests that studies aiming to identify differences between interface and non interface residues should consider a more restrict definition of interface, where free energy differences due to binding should be taken on consideration.  aBioinformatics  aBioinformática  aEstruturas monoméricas  aHot spots  aPropriedades físicas  aPropriedades químicas  aResíduos de interface  aResíduos superficiais1 aTOZZI, C. L.