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Webinar

HIV at a distance away: DEER EPR spectroscopy applied towards the understanding of HIV reverse transcriptase and HIV protease inhibitors.

October 4th, 16:00 CEST

Key Learning Points

  • Exploring the use of DEER spectroscopy in structural and conformational studies of biological molecules in the evaluation of potential drug targets
  • Description of the technique, including sample preparation, experimental requirements, spectroscopic methods, as well as a brief comparison with other structural elucidation techniques
  • Analysis and interpretation of the data to develop models for the evaluation of drug targets
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Who Should Attend?

The webinar is geared to anyone interested in applying structural and conformational studies of proteins in the targeted evaluation of potential medications. This audience would include scientists in the pharmaceutical industry as well in academic and government laboratories.

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Summary

Pulsed double electron–electron resonance (DEER) EPR spectroscopy provides a means of accurately measuring long-range distances, offering an invaluable tool for conformational analysis of biological macromolecules. While DEER spectroscopy is not commonly used for drug evaluation, new methods provide great promise towards its implementation and success where other biophysical methods may not succeed.

Here we show the realization of DEER spectroscopy towards potential drug targets of HIV-1 reverse transcriptase and subsequently its catalytic partner HIV protease. Specifically, the understanding of the asymmetric arrangement of the HIV reverse transcriptase precursor permitted a targeted evaluation of known drugs to prevent its arrest and its maturation towards its biological active form by HIV protease. Subsequently, HIV protease was presented to various known drugs to understand molecular arrangement upon drug association. Overall, DEER holds great promise to rapidly evaluate molecular interactions that will ultimately allow it to target a wide range of diseases and their molecular mechanisms.

Speakers

Thomas Schmidt, Ph.D.

National Institutes of Health

Dr. Schmidt is originally from Germany at which point he migrated to the US to do his undergraduate studies at California State University, Northridge. During this time he developed a taste for magnetic resonance under the guidance of Dr. Karin Crowhurst. During his doctoral studies in NMRm, Dr. Schmidt developed the understanding of Platelet integrin αIIbβ3 signaling and its subsequent regulation by its transmembrane domains under the guidance of Dr. Tobias Ulmer at the University of Southern California. His postdoctoral studies maneuvered Dr. Schmidt to the National Institutes of Health under the guidance of Dr. Marius Clore to deploy pulse EPR to understand the molecular mechanism of HIV reverse transcriptase maturation by HIV protease.