Key Learning Points
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.
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.
Thomas Schmidt, Ph.D.
National Institutes of Health