Work Groups for Structural Analysis

A key step for drug development is an understanding of structural properties of the molecular binding mode in particular. To better resolve the dynamic behaviour of transient binding pockets four different biophysical methods are in use addressing the distinguished instability of elusive binding pockets.

A1 Dötsch: Bio-NMR

Transient binding pockets are elusive and highly dynamic. These properties can be detected and evaluated by NMR spectroscopy. Therefore, NMR spectroscopy enables Prof. Dötsch and his coworkers to identify transient binding pockets in vitro and in vivo.

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A2 Knapp & von Delft: Crystallography

High resolution data of ligand complexes are ideal to evaluate and optimize these complexes. Prof. Knapp will work together with Diamond Synchrotron (https://www.diamond.ac.uk/Instruments/Mx/I04-1/Staff/von-Delft.html) and the group of Prof. Frank von Delft to find new ligands for transient binding pockets making use of established crystallographic high-throughput methods.

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A3 Hänelt: Electron Spin Resonance Spectroscopy

Electron spin resonance (ESR) spectroscopy allows the evaluation of diverse information about locally labeled proteins, like folding dynamics. Within the TRABITA project Prof. Hänelt and her coworkers will uncover specific ligands, and they will investigate ligand-dependent protein dynamics . Furthermore, ESR will become an established screening method for conformationally specific ligands over the course of TRABITA.

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A4 Lermyte: Conformation-Sensitive Mass Spectrometry

Modern high-resolution mass spectrometry has opened up new vistas in protein analysis. Strategies such as hydrogen-deuterium exchange make it possible to “encode” information on protein folding and dynamics in solution. “Native” MS allows the analysis of intact noncovalent complexes in the gas phase, while ion mobility analysis provides information on protein conformation, and top-down fragmentation can be used to determine the sequence of component monomers.

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