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Project

Long-term observation and correlation of protein dynamics using combined single-molecule measurements

The conformational dynamics of proteins are essential for their functioning in both life and disease. Yet it remains difficult to experimentally determine the manifold of accessible conformations, lifetimes, and transitions. Single-molecule FRET (smFRET) likely is the most suitable technique available due to its ability to function at ambient conditions and to avoid ensemble averaging. Yet the technique is challenged by the short observation times and the difficulty in measuring more than one molecular distance at the same time.

Our goal is to develop an innovative approach that extends the strengths of smFRET to much longer observation durations while also providing integration of multiple measurements into a coherent molecular picture. We will do so by integrating smFRET measurements with electrophysiology, combining the speed and sensitivity of electrical readout with accurate distance measurements. This innovative concept will deliver a capability that is not available elsewhere. The resulting methodology will be applied to map the conformational dynamics of a class of clinically-important proteins, and to reconstructing the conformational- and association-based events associated with an important bacterial membrane transporter and model system for eukaryotic sorting machinery. We expect that this project will allow us to develop our innovative methodology and claim the novelty of the concept.

Date:1 Jan 2022 →  Today
Keywords:protein dynamics
Disciplines:Molecular biophysics, Spectroscopic methods, Electrophysiology