Self-replication molecules design

The design of self-replicating molecules, M. M. Conn and J. Rebek, Jr., Curr. Opin. Struct. Biol., 1994, 4, 629. 

Scheme 1-15 Self-replicating system designed by Rebek and co-workers. The template 57 (X = OCgF5) binds to the two substrates 55 and 56, generating a ternary complex 55-57-S6. Then 55 and 56 react to generate another molecule of template 57. Stability constants are shown for the 55-56 and 57-57 complexes.

Such models can be developed for the computational design of catalytic sterns that self organize and adapt themselves for optimum catalytic performance. Adaptation occurs in the reproduction process with mutation of the self-replicating molecules coupled to the metabolic system. The metabolic system acts as the bio-immune molecular recognition and response system. The conditions for the emergence of such a stem are far from equilibrium in the complex regime. The behavior as a function of time is unpredictable, similar to the class 4 system proposed by Wolfram. 

RNA has proven to be a remarkably malleable tool in the hands of biochemists, and a satisfactory RNA-dependent RNA polymerase ribozyme will probably be developed in the laboratory eventually. When that happens, it will be the culmination of at least a decade s worth of directed efforts, using complex combinations of rational design and in vitro evolution. It will be an important demonstration that further strengthens the case that an RNA World could have existed, but it will also show that RNA polymerase ribozymes do not appear to be a simple functionality that is likely to appear de novo from a naive population of RNA molecules. The possibility of a self-replicating RNA system less sophisticated than a general RNA-dependent RNA polymerase ribozyme cannot be eliminated. 

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