By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function.

It is well established that gene regulation can be achieved through activator and repressor proteins that bind to DNA and switch particular genes on or off, and that complex metabolic networks determine the levels of transcription of a given gene at a given time. Using three complementary computational techniques to study the sequence-dependence of DNA denaturation within DNA minicircles, we have observed that whenever the ends of the DNA are constrained, information can be transferred over long distances directly by the transmission of mechanical stress through the DNA itself, without any requirement for external signalling factors. Our models combine atomistic molecular dynamics (MD) with coarse-grained simulations and statistical mechanical calculations to span three distinct spatial resolutions and timescale regimes. While they give a consensus view of the non-locality of sequence-dependent denaturation in highly bent and supercoiled DNA loops, each also reveals a unique aspect of long-range informational transfer that occurs as a result of restraining the DNA within the closed loop of the minicircles.

Tin(IV) oxide (SnO₂) is a promising electron transport layer for n-i-p perovskite solar cells (PSCs) due to its high transmittance, excellent charge mobility, and strong chemical stability. However, surface defects such as oxygen vacancies and hydroxyl groups at the SnO₂/perovskite interface degrade the device performance by increasing carrier recombination and accelerating degradation. While alkali halide salts offer a simple yet effective method for passivation, their enhancement mechanisms at the atomic level remain unclear, as most studies focus on bulk or surface effects rather than the heterointerface itself. Here, we introduce a potassium halide salt (PHS: KI, KCl, and KI+KCl) post-treatment to passivate the SnO₂/MAPbI₃ interface. Our combined experimental and density functional theory (DFT) analyses demonstrate that K⁺ and halide ions facilitate the removal of oxygen vacancies and extrinsic hydroxyl groups through the formation of KOH. This process effectively reduces the bond strength of surface hydroxyls and enhances interfacial ordering. This results in a smoother interface, larger perovskite grain sizes, improved adhesion, and enhanced charge extraction. The formation of Sn-Cl-Pb and Sn-I-Pb bonds, along with electrostatic interactions among interfacial K⁺, I^- in the perovskite structure, and O^2- in SnO₂, strengthens the interface and reduces ion migration. KI-modified and mixed KI+KCl devices achieved power conversion efficiencies (PCEs) of 19.86% and 19.15%, respectively, outperforming untreated SnO₂, which had a PCE of 18.41%. More importantly, the mixed KI+KCl treatment shows superior stability improvement compared to individual PHS treatments, retaining over 96% of the initial PCE after 1000 h under 40-50% relative humidity. These findings highlight the critical role of potassium salts in improving both efficiency and stability, offering an effective strategy for advancing PSC technology.

Human topoisomerase 1B has been simulated covalently bound to a negatively supercoiled DNA minicircle, and its behavior compared to the enzyme bound to a simple linear DNA duplex. The presence of the more realistic supercoiled substrate facilitates the formation of larger number of protein-DNA interactions when compared to a simple linear duplex fragment. The number of protein-DNA hydrogen bonds doubles in proximity to the active site, affecting all of the residues in the catalytic pentad. The clamp over the DNA, characterized by the salt bridge between Lys369 and Glu497, undergoes reduced fluctuations when bound to the supercoiled minicircle. The linker domain of the enzyme, which is implicated in the controlled relaxation of superhelical stress, also displays an increased number of contacts with the minicircle compared to linear DNA. Finally, the more complex topology of the supercoiled DNA minicircle gives rise to a secondary DNA binding site involving four residues located on subdomain III. The simulation trajectories reveal significant changes in the interactions between the enzyme and the DNA for the more complex DNA topology, which are consistent with the experimental observation that the protein has a preference for binding to supercoiled DNA.

DNA supercoiling results in compacted DNA structures that can bring distal sites into close proximity. It also changes the local structure of the DNA, which can in turn influence the way it is recognised by drugs, other nucleic acids and proteins. Here, we discuss how DNA supercoiling and the formation of complex DNA topologies can affect the thermodynamics of DNA recognition. We then speculate on the implications for transcriptional control and the three-dimensional organisation of the genetic material, using examples from our own simulations and from the literature. We introduce and discuss the concept of coupling between the multiple length-scales associated with hierarchical nuclear structural organisation through DNA supercoiling and topology.

The selectivity of electrochemical sensors to ascorbic acid (AA), dopamine (DA), and uric acid (UA) remains an open challenge in the field of biosensing. In this study, the selective mechanisms for detecting AA, DA, and UA molecules on the graphene and graphene oxide substrates were illustrated through the charge population analysis from the density functional theory (DFT) calculation results. Our substrate models contained the 1:10 oxygen per carbon ratio of reduced graphene oxide, and the functionalized configurations were selected according to the formation energy. Geometry optimizations were performed for the AA, DA, and UA on the pristine graphene, epoxy-functionalized graphene, and hydroxyl-functionalized graphene at the DFT level with vdW-DF2 corrections. From the calculations, AA was bound to both epoxy and hydroxyl-functionalized GO with relatively low adsorption energy, while DA was adsorbed stronger to the electronegative epoxy groups. The strongest adsorption of UA to both functional groups corresponded to the largest amount of electron transfer through the pi orbitals. Local electron loss created local electric fields that opposed the electron transfer during an oxidation reaction. Our analysis agreed with the results from previous experimental studies and provided insight into other electrode modifications for electrochemical sensing.