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From Next Generation DNA Sequencing to the Novel Characterization of Biomolecular Fluctuations

Nanoscale devices that address or detect individual molecules offer a new paradigm for sensing and have the potential to revolutionize a broad range of industries, from healthcare to defense. I will discuss two examples where nanoscale sensing is poised to significantly impact basic science and applications.

The first is a sequencing platform based on the measurement of transverse electronic currents during the translocation of single-stranded DNA through nanopores. Using molecular dynamics simulations coupled to quantum mechanical calculations of the tunneling current, I will show that the DNA nucleotides are predicted to have distinguishable electronic signatures in experimentally realizable systems. Several recent experiments support our theoretical predictions and demonstrate that this method may help usher in an era of personalized medicine, where genetic information is used to diagnose, treat, and prevent diseases. Moreover, nanopores offer an ideal testing ground to study open scientific issues in the relatively unexplored area at the interface between solids, liquids, and biomolecules at the nanometer length scale.

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The second is a novel technique to characterize structural transitions and fluctuations in biological molecules. Structural transitions appear everywhere: proteins fold, nanotubes collapse, DNA denatures, ice melts, and so on. In biology, these transitions play a role in processes such as transcription and also determine protein function. Yet, at the same time, they give examples of highly nonlinear processes that are challenging to model and understand. I will discuss how thermal transport is intimately tied to the nonlinear fluctuations that ultimately result in conformational changes. Thermal transport thus provides an innovative method to probe structural transitions in biomolecules and materials, and may also give opportunities for developing thermal devices for use in, e.g., medical diagnostics.

Sponsors

james.liddle [at] nist.gov (J. Alex Liddle), 301-975-6050

Michael Zwolak

Department of Physics, Oregon State University

Created August 31, 2014, Updated September 21, 2016