combinatorial complexity and compositional drift in protein interaction networks组合的复杂性和成分漂移的蛋白质相互作用网络.pdf

Combinatorial Complexity and Compositional Drift in Protein Interaction Networks 1 2 ´ ˆ 3 4 5 Eric J. Deeds , Jean Krivine , Jerome Feret , Vincent Danos , Walter Fontana * ´ 1 Center for Bioinformatics and Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, United States of America, 2 Laboratoire PPS de l’Universite ´ ´ ´ Paris 7 and CNRS, F-75230 Paris, France, 3 Laboratoire d’Informatique de l’Ecole normale superieure, INRIA, ENS, and CNRS, F-75230 Paris, France, 4 School of Informatics, University of Edinburgh, Edinburgh, United Kingdom, 5 Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America Abstract The assembly of molecular machines and transient signaling complexes does not typically occur under circumstances in which the appropriate proteins are isolated from all others present in the cell. Rather, assembly must proceed in the context of large-scale protein-protein interaction (PPI) networks that are characterized both by conflict and combinatorial complexity. Conflict refers to the fact that protein interfaces can often bind many different partners in a mutually exclusive way, while combinatorial complexity refers to the explosion in the number of distinct complexes that can be formed by a network of binding possibilities. Using computational models, we explore the consequences of these characterist