title: Global view of the protein universe.
abstract: To explore protein space from a global perspective, we consider 9,710 SCOP (Structural Classification of Proteins) domains with up to 70% sequence identity and present all similarities among them as networks: In the "domain network," nodes represent domains, and edges connect domains that share "motifs," i.e., significantly sized segments of similar sequence and structure. We explore the dependence of the network on the thresholds that define the evolutionary relatedness of the domains. At excessively strict thresholds the network falls apart completely; for very lax thresholds, there are network paths between virtually all domains. Interestingly, at intermediate thresholds the network constitutes two regions that can be described as "continuous" versus "discrete." The continuous region comprises a large connected component, dominated by domains with alternating alpha and beta elements, and the discrete region includes the rest of the domains in isolated islands, each generally corresponding to a fold. We also construct the "motif network," in which nodes represent recurring motifs, and edges connect motifs that appear in the same domain. This network also features a large and highly connected component of motifs that originate from domains with alternating alpha/beta elements (and some all-alpha domains), and smaller isolated islands. Indeed, the motif network suggests that nature reuses such motifs extensively. The networks suggest evolutionary paths between domains and give hints about protein evolution and the underlying biophysics. They provide natural means of organizing protein space, and could be useful for the development of strategies for protein search and design.
authors: Department of Computer Science and Engineering, Polytechnic Institute of New York University, Brooklyn, NY 11201;
authors: Sergey
authors: S
authors: Nepomnyachiy
authors: Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel; and bental@ashtoret.tau.ac.il trachel@cs.haifa.ac.il.
authors: Nir
authors: N
authors: Ben-Tal
authors: Department of Computer Science, University of Haifa, Mount Carmel 31905, Israel bental@ashtoret.tau.ac.il trachel@cs.haifa.ac.il.
authors: Rachel
authors: R
authors: Kolodny
mesh_terms: D020816:Amino Acid Motifs; D055592:Biophysical Phenomena; D030562:Databases, Protein; D019143:Evolution, Molecular; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D040681:Structural Homology, Protein
chemical_list: D011506:Proteins
keywords: protein cooccurrence networks; protein similarity networks