title: SH2 binding site comparison: a new application of the SURFCOMP method.
abstract: To avoid side effects, it is often desirable to increase the specificity of a drug candidate when targeting one member of a family of related proteins, whereby one exploits small differences between the structures of the binding sites. Identification of such differences can be carried out by analyzing the distributions of physicochemical properties mapped onto molecular surfaces. Here we demonstrate that SURFCOMP, our local surface similarity detection method, is able to detect differences between the binding sites of two closely related proteins. We analyzed the SH2 domains of Sap and Eat-2, two highly similar signal transduction molecules involved in inflammatory processes and found differences between their binding sites that can possibly lead to a better understanding of the different specificities of the two proteins.
authors.affiliation: In Silico Sciences Unit, Informatics and Knowledge Management, Novartis Institutes for BioMedical Research Vienna, Brunnerstrasse 59, A-1235 Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Hofbauer
authors.forename: András
authors.initials: A
authors.lastname: Aszódi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D012984:Software; D040681:Structural Homology, Protein; D013912:Threonine / Q000378:metabolism; D014633:Valine / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D008024:Ligands; D011506:Proteins; D013912:Threonine; D014633:Valine