From ligand–receptor binding to DNA hybridization, molecular recognition plays a central role in biology. Over the past several decades, chemists have successfully reproduced the exquisite specificity of biomolecular interactions. However, engineering multiple specific interactions in synthetic systems remains difficult. DNA retains its position as the best medium with which to create orthogonal, isoenergetic interactions, based on the complementarity of Watson–Crick binding. Here we show that DNA can be used to create diverse bonds using an entirely different principle: the geometric arrangement of blunt-end stacking interactions. We show that both binary codes and shape complementarity can serve as a basis for such stacking bonds, and explore their specificity, thermodynamics and binding rules. Orthogonal stacking bonds were used to connect five distinct DNA origami. This work, which demonstrates how a single attractive interaction can be developed to create diverse bonds, may guide strategies for molecular recognition in systems beyond DNA nanostructures.
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The authors gratefully acknowledge financial support for the Molecular Programming Project from the US National Science Foundation for Expeditions in Computing (No. 0832824, http://molecular-programming.org) and the Computer and Communication Foundations Emerging Models and Technologies grants No. 0829951 and No. 0622254, the Semiconductor Research Corporation Focus Center on Functional Engineered Nano Architectonics, the Microsoft Corporation and Mark Sims of Nanorex Corporation. S.W. thanks the Benjamin M. Rosen Family Foundation for a graduate fellowship. The authors thank the DNA and Natural Algorithms laboratory, and in particular L. Qian, N. Dabby, D. Doty, R. Schulman and J. Szablowski for comments.
The authors declare no competing financial interests.
Supplementary information (PDF 4602 kb)
Computer program codes for designing bond types (MATLAB files) (ZIP 878 kb)
Installer for modified caDNAno program (ZIP 757 kb)
caDNAno design files for shape systems (origami A,B,C, and D) and corner origami designs (ZIP 422 kb)
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Woo, S., Rothemund, P. Programmable molecular recognition based on the geometry of DNA nanostructures. Nature Chem 3, 620–627 (2011). https://doi.org/10.1038/nchem.1070
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