Sie sind hier: Startseite Aktuelles Termine-Vorträge Dr. Sonja Schmid, Kavli Institute …

Dr. Sonja Schmid, Kavli Institute of Nanoscience, TU Delft, NL

Single Protein Dynamics: from Fluorescence to Electrical Detection
Wann 01.07.2019
von 13:30 bis 14:30
Wo Hörsaal Physikalische Chemie, Albertstr. 23 a
Termin übernehmen vCal
iCal

Proteins are the molecular makers in our body. They use diverse energy sources to perform specific tasks in a highly controlled and efficient manner. For an in-depth understanding of the energetics and diverse driving forces that govern protein machines, we still lack detailed, dynamic information on the molecular level.
Single molecule FRET is amongst the most popular biophysical techniques to observe individual proteins at work in real time. However, due to photo-bleaching, the observation time of one single molecule spans hardly more than 2 orders of magnitude, e.g. 10ms - 1s, or 1s - 100s. This makes quantitative kinetic analysis challenging. I will present here our solution to the challenge: a 2D machine-learning approach that extracts a
maximum of information out of inherently noisy single-molecule trajectories. It has allowed us to pinpoint
remarkable, mechanistic effects of the Hsp90 chaperone system, i.a. induced by a co-chaperone, drug
candidates, macro-molecular crowding, or mutations.
Despite all experimental and analytical efforts, the time bandwidth of single-molecule fluorescence
remains poor compared to protein dynamics occurring on much broader timescales simultaneously. An
advantageous alternative is therefore electrical detection, spanning microseconds to hours in one
experiment. We exploit this in an entirely new approach to protein kinetics, using a combination of solidstate
nanopores with DNA origami. Specifically, we anchor the protein of interest to a DNA origami
structure inside a nanopore and monitor its behavior electrically, by means of conductance changes
over time. I will discuss our latest results obtained with this new & label-free single protein detector. In
combination with existing 3D structures and MD simulations, it has the potential to reveal the kinetic &
energetic origin of protein function at the sub-molecular level.

 

Organisation:
Physikalisch-Chemisches Kolloquium
Institut für Physikalische Chemie