1994) Chemical properties of the modeled replicator such as grow

1994). Chemical properties of the modeled replicator such as growth/decay rates and catalytic capacity depend on RNA secondary structure (and active sites). We study the evolution of a system, initialized with a population of random sequences, towards two target structures assumed to have a specific catalytic activity. After a very long lag phase where non-functional replicators dominate the system, we observe a rapid transition towards metabolic cooperation of catalytically functional molecules. We conclude that partial compartmentalization by absorption

on a surface, together with the neutrality in sequence-structure find protocol folding, suffices to enable the spontaneous and irreversible discovery of the first major transition. Gilbert, W.: 1986, The RNA World, Nature 319, 618. Joyce, G. F. and Orgel, L. E.: 1999, Prospects for Understanding the Origin of the RNA World, in Gesteland, R.

F., Cech, T. R. and Atkins, J. F. (eds), The RNA World, pp. 49–77, Cold Spring Harbor Lab. Press, Cold Spring Harbor. Maynard Smith, J. and Szathmáry, E.: 1995, The Major Transitions in Evolution, Freeman, Spektrum, Oxford. Schuster P., Fontana, W., Stadler, P.F. and Hofacker, I.L.,1994, From sequences to learn more shapes and back: a case study in RNA secondary structures. Proc. Royal Society London B, 255:, 279–284. E-mail: sergio.​branciamore@unifi.​it A Kinase Ribozyme that 17-DMAG (Alvespimycin) HCl Self-Phosphorylates at Two Different Sites 1Elisa Biondi, 2David Nickens, 3James Patterson, 1,3Dayal Saran, 1Donald Burke 1Department of Molecular Microbiology & Immunology and Department of Biochemistry, University of Missouri School of Medicine, 1201 E. Rollins St., Columbia, MO 65211-7310; 2Department of Biology, Indiana University, Bloomington, IN, 47405;

3Department of Chemistry, Indiana University, Bloomington, IN, 47405 Our long-term goal is to understand the catalytic potential of RNA, the feasibility of RNA-based evolution in an RNA World, and the possibility of using RNA to engineer artificial gene regulation and metabolism. A key constraint in the acquisition of new biochemical function is the interplay between substrate binding and catalysis. Simply put, active sites within metabolic ribozymes must accommodate diffusible substrates. We are analyzing the mechanism of action and catalytic requirements of kinase ribozymes. RNA-catalyzed phosphorylations are attractive to study for several reasons. First, phosphoryl transfer is one of the most important and ubiquitous reactions in small molecule and protein metabolism, and of fundamental biological and evolutionary significance. Second, the chemical mechanism of many natural kinases have been studied extensively, facilitating comparison of ribozyme and protein catalysis of equivalent reactions.

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