an evolutionary trace method defines binding surfaces common to protein families（进化的跟踪方法定义绑定表面常见的蛋白质家族）.pdfVIP

J. Mol. Biol. (1996) 257, 342–358 An Evolutionary Trace Method Defines Binding Surfaces Common to Protein Families Olivier Lichtarge1,2, Henry R. Bourne1 and Fred E. Cohen1,2* 1Departments of Cellular and X-ray or NMR structures of proteins are often derived without their Molecular Pharmacology and ligands, and even when the structure of a full complex is available, the area Medicine and 2Department of of contact that is functionally and energetically significant may be a Pharmaceutical Chemistry specialized subset of the geometric interface deduced from the spatial University of California proximity between ligands. Thus, even after a structure is solved, it San Francisco remains a major theoretical and experimental goal to localize protein CA 94143-0450, USA functional interfaces and understand the role of their constituent residues. The evolutionary trace method is a systematic, transparent and novel predictive technique that identifies active sites and functional interfaces in proteins with known structure. It is based on the extraction of functionally important residues from sequence conservation patterns in homologous proteins, and on their mapping onto the protein surface to generate clusters identifying functional interfaces. The SH2 and SH3 modular signaling domains and the DNA binding domain of the nuclear hormone recep