Apr 8, 2025
2:30pm - 2:45pm
Summit, Level 3, Room 333
Arpan De1,Arindam Das2,M. P. Anantram1
University of Washington1,Eastern Washington University2
The structural attributes of RNA, especially co-transcriptional folding, have enabled RNA origami to construct complex 3D architecture, serving as a platform for building RNA-based nanodevices. However, the potentiality of RNA in molecular electronics is largely unexplored, mainly due to its inherent conformational fluctuations. This variability poses challenges but also offers opportunities for tuning RNA-based molecular devices by exploiting their dynamic nature. Here, we have reported a comprehensive analysis of how conformational fluctuations impact ssRNA charge transport, thus explaining the experimentally obtained conductance stochasticity in ssRNA.
In this study, we systematically explored the charge transport properties of a short (10-base) single-stranded RNA. We started by comparing the structural stability of single- and double-stranded RNAs. The comparison used three key metrics: 1D- and 2D-RMSDs, end-to-end phosphorous distance (△P
dis), and backbone dihedral angles. Our analysis revealed that dsRNA exhibits greater stability in the three metrics, highlighting the potential for large conformational fluctuations in ssRNA. The superior stability of dsRNA is well known to be due to intra-base pair hydrogen bonding. In ssRNA sequences, hydrogen bonding between adjacent bases plays a critical role in programming their folding probabilities, offering a potential design rule for manipulating ssRNA structures. The significant spread of the conductance spectrum (~ 10
3 G
0) points to the strong influence of conformational fluctuations on ssRNA charge transport. While conductance tends to increase with lower △P
dis, the wide spread of conductances across all △P
dis categories underscore the importance of nucleotide positioning. A strong correlation between the delocalization of both HOMO and HOMO-1 orbitals with △P
dis values was observed. These observations suggest while △P
dis is a global factor influencing ssRNA conductance trends, inter-base distances locally modulate charge transport. To substantiate this hypothesis, we proposed a new metric,
probable pathways, taking into account: orbital delocalization, density of states, and proximity between nucleotides. These pathways offer insight into the striking conductance differences among conformations. Efficient charge transport favors shorter hopping distances and higher availability of states in the hopping sites, with the former having more weight. Thus, while pathways in folded structures are governed by inter-base distances, those in unfolded structures depend more on the density of states delocalization. We further validated the concept of
proposed pathways by analyzing conductance drops when these pathways are disrupted. Finally, we explored practical approaches to harness ssRNA structural fluctuations, reducing conductance stochasticity. We demonstrated that higher salt concentrations stabilize ssRNA.
Our findings reveal the dramatic conductance fluctuations between folded and unfolded states and highlight the potential to achieve two distinct conductance states through controlled manipulation of ssRNA unfolding and refolding. To this end, state-of-the-art techniques such as optical and magnetic tweezers present promising methods to reversibly switch ssRNA between these two conformational states. This opens up the possibility of building
electrically readable, biodegradable, highly scalable logic circuits, and switches. Additionally, regulating salt concentrations offers a viable strategy to limit conformational fluctuations, ensuring more deterministic performance in applications. We anticipate that the outcomes of this study will inspire future experimental research to harness the high and low conductivity of ssRNA in its folded and unfolded states, thus contributing to the advancement of molecular bioelectronics.