An ability to rationally design complex networks from the bottom up can offer valuable quantitative model systems for use in gaining a deeper appreciation for the principles governing the self-organization and functional characteristics of complex systems. We report herein the de novo design, graph prediction, experimental analysis, and characterization of simple self-organized, nonlinear molecular networks. Our approach makes use of the sequence-dependant auto- and cross-catalytic functional characteristics of template-directed peptide fragment condensation reactions in neutral aqueous solutions. Starting with an array of 81 sequence similar 32-residue coiled-coil peptides, we estimated the relative stability difference between all plausible A ₂ B-type coiled-coil ensembles and used this information to predict the auto- and cross-catalysis pathways and the resulting plausible network motif and connectivities. Similar to most complex systems, the generated graph displays clustered nodes with an overall hierarchical architecture. To test the validity of the design principles used, nine nodes composing a main segment of the graph were experimentally analyzed for their capacity in establishing the predicted network connectivity. The resulting self-organized chemical network is shown to display 25 directed edges in good agreement with the graph analysis estimations. Moreover, we show that by varying the system parameters (presence or absence of certain substrates or templates), its operating network motif can be altered, even to the extremes of turning pathways on or off. We suggest that this approach can be expanded for the construction of large-scale networks, offering a means to study and to understand better the emergent, collective behaviors of networks.

Adaptable DNA Analogs: The defining feature of DNA as a genetic blueprint is its capacity for self-replication. In the cell, however, the replication process requires the assistance of multiple elaborate enzymes. How then at the origin of life could DNA or its precursor replicate before enzymes were present? Ura et al. (p. 73 , published online 11 June) have achieved the long-sought goal of preparing a synthetic DNA analog that can dynamically adapt its sequence in free solution. Their analog (as yet only studied in relatively short, 20-unit oligomers) replaces DNA's sugar and phosphate backbone by a peptide strand in which cysteines reversibly bind the conventional DNA bases through thioester tethers. These strands can pair with complementary sequences of true DNA and furthermore swap one tethered base for another if different DNA templating strands are added to the solution in succession.