Programming Biomolecular Self-Assembly Pathways
Peng Yin1, Harry M.T. Choi2, Colby R. Calvert2 and Niles A. Pierce3, (1)Computer science, bioengineering, Caltech, Pasadena, CA, (2)Bioengineering, Caltech, Pasadena, CA, (3)Bioengineering, Applied & Computational Mathematics, Caltech, Pasadena, CA

We will present our recent work (Nature, 451:318-322, 2008) that introduces a layered abstraction framework and a rudimentary programming language for directing the dynamic behavior of synthetic biomolecular systems. In nature, self-assembling and disassembling complexes of proteins and nucleic acids bound to a variety of ligands perform intricate and diverse dynamic functions. In contrast, attempts to rationally encode structure and function into synthetic amino acid and nucleic acid sequences have largely focused on engineering molecules that self-assemble into prescribed target structures, rather than on engineering transient system dynamics. To design systems that perform dynamic functions without human intervention, it is necessary to encode within the biopolymer sequences the reaction pathways by which self-assembly occurs. Here, we program diverse molecular self-assembly and disassembly pathways using a ‘reaction graph' abstraction to specify complementarity relationships between modular domains in a versatile DNA hairpin motif. Molecular programs are executed for a variety of dynamic functions: catalytic formation of branched junctions, autocatalytic duplex formation by a cross-catalytic circuit, nucleated dendritic growth of a binary molecular ‘tree', and autonomous locomotion of a bipedal walker.

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Molecules and Macromolecules to Systems

The Preliminary Program for SBE's 2nd International Conference on Biomolecular Engineering