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Abstract Allostery is a hallmark of cellular function and important in every biological system. Still, we are only starting to mimic it in the laboratory. Here, we introduce an approach to study aspects of allostery in artificial systems. We use a DNA origami domino array structure which–upon binding of trigger DNA strands–undergoes a stepwise allosteric conformational change. Using two FRET probes placed at specific positions in the DNA origami, we zoom in into single steps of this reaction cascade. Most of the steps are strongly coupled temporally and occur simultaneously. Introduction of activation energy barriers between different intermediate states alters this coupling and induces a time delay. We then apply these approaches to release a cargo DNA strand at a predefined step in the reaction cascade to demonstrate the applicability of this concept in tunable cascades of mechanochemical coupling with both spatial and temporal control. 

The characteristics of the interface between DNA and metallic carbon nanotube (CNT) in supramolecular assemblies are important to understand for electronic and sensing applications. We study the mechanical stability and electronic properties of these interfaces with amino and ester linkers using computational experiments. Our study demonstrates that both linkers significantly enhance the mechanical stability of DNA–CNT systems, with the DNA adopting a stable and lower energy perpendicular orientation relative to the CNT as opposed to a conventional parallel arrangement. This lower energy configuration is driven by nonbonded interactions between the DNA base and the CNT surface. Our calculations also reveal that interface resistance is primarily governed by DNA–CNT interactions with negligible contribution from the linkers. In the case of the amino linker, we predict a 100-fold transmission ratio between parallel and perpendicular configurations of DNA relative to CNT. This observation can be used to build an electromechanical switch with fast switching times (30 ns). The ester linker, on the contrary, enables a better electronic coupling between the DNA and CNT even when strained. 

Aptamer binding to DNA increases conductance over tenfold, enabling high-resistance contrast DNA strands for molecular electronics development. 

This article explores how conformational fluctuations influence the conductance of a single-stranded RNA (ssRNA) and the means to harness its inherent structural variabilityviasalt concentration regulation. 

The global COVID-19 pandemic has highlighted the need for rapid, reliable, and efficient detection of biological agents and the necessity of tracking changes in genetic material as new SARS-CoV-2 variants emerge. Here we demonstrate that RNA-based, single-molecule conductance experiments can be used to identify specific variants of SARS-CoV-2. To this end, we i) select target sequences of interest for specific variants, ii) utilize single-molecule break junction measurements to obtain conductance histograms for each sequence and its potential mutations, and iii) employ the XGBoost machine learning classifier to rapidly identify the presence of target molecules in solution with a limited number of conductance traces. This approach allows high-specificity and high-sensitivity detection of RNA target sequences less than 20 base pairs in length by utilizing a complementary DNA probe capable of binding to the specific target. We use this approach to directly detect SARS-CoV-2 variants of concerns B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron) and further demonstrate that the specific sequence conductance is sensitive to nucleotide mismatches, thus broadening the identification capabilities of the system. Thus, our experimental methodology detects specific SARS-CoV-2 variants, as well as recognizes the emergence of new variants as they arise.