A measure of bending in nucleic acids structures applied to A-tract DNA

A method is proposed to measure global bending in DNA and RNA structures. It relies on a properly defined averaging of base-fixed coordinate frames, computes mean frames of suitably chosen groups of bases and uses these mean frames to evaluate bending. The method is applied to DNA A-tracts, known to induce considerable bend to the double helix. We performed atomistic molecular dynamics simulations of sequences containing the A4T4 and T4A4 tracts, in a single copy and in two copies phased with the helical repeat. Various temperature and salt conditions were investigated. Our simulations indicate bending by roughly 10° per A4T4 tract into the minor groove, and an essentially straight structure containing T4A4, in agreement with electrophoretic mobility data. In contrast, we show that the published NMR structures of analogous sequences containing A4T4 and T4A4 tracts are significantly bent into the minor groove for both sequences, although bending is less pronounced for the T4A4 containing sequence. The bending magnitudes obtained by frame averaging are confirmed by the analysis of superhelices composed of repeated tract monomers

A Route to Superior Performance of a Nanoplasmonic Biosensor: Consideration of Both Photonic and Mass Transport Aspects

Optical biosensors based on plasmonic nanostructures present a promising alternative to conventional biosensing methods and provide unmatched possibilities for miniaturization and high-throughput analysis. Previous works on the topic, however, have been overwhelmingly directed toward elucidating the optical performance of such sensors, with little emphasis on the topic of mass transport. To date, there exists no examination, experimental nor theoretical, of the bioanalytical performance of such sensors (in terms of detection limits) that simultaneously addresses both optical and mass transport aspects in a quantitative manner. In this work we present a universal model that describes the smallest concentration that can be detected by a nanoplasmonic biosensor. Accounting for both optical and mass transport aspects, this model establishes a relationship between bioanalytical performance and the biosensor’s design parameters. We employ the model to optimize the performance of a nanoplasmonic DNA biosensor consisting of randomly distributed gold nanorods on a glass substrate. Through both experimental and theoretical results, we show that the proper design of a nanostructured sensing substrate is one that maximizes mass transport efficiency while preserving the quality of the optical readout. All results are compared with those obtained using a conventional SPR biosensor. We show that an optimized nanoplasmonic substrate allows for the detection of DNA at concentrations of an order of magnitude lower with respect to an SPR biosensor