Structural Biology at FMP

Molecular pharmacology requires structural information on all length and time scales. Contributions of NMR spectroscopy typically include high-resolution structural investigations on target systems, studies of their interactions with drug-like molecules, and imaging at the level of organisms. As a spectroscopic technique, NMR serves ‘metabolomics’ studies and investigations on the effects of dynamics in biological processes. Future pharmacology-oriented structural studies are expected to provide information on how super-molecular arrangements assemble and disassemble within the cell, and how these processes are controlled in vivo by protein expression, degradation, post-translational modification as well as through the application of small-molecule or protein-based drugs. The dynamic nature of these phenomena demands the application of NMR, exploiting its triple capabilities of structure determination, spectroscopy, and imaging. Integrating these and other biophysical data with molecular modelling and cheminformatics methods is essential for deriving a comprehensive picture of pharmacological processes as a basis for ligand design.

Current work in the section pursues research projects along two major avenues:

(1) Structural investigations in physiological environments from atomic resolution to imaging

Research topics cover the application of NMR to living cells (Selenko) and methods development for enhancing NMR signals in complex samples using hyperpolarisation methods (Oschkinat). In addition, new types of contrast agents in magnetic resonance imaging (MRI) are generated by molecule-specific hyperpolarisation (Schröder).

(2) Systematic development of bioactive molecules

This effort is supported by conventional structure determination approaches employing NMR as well as X-ray crystallography, the latter in collaboration with Heinemann, Daumke at the Max-Delbrück-Centre. Topics comprise the design and screening of small-molecule compound libraries (Kühne), rational design of bioactive compounds that modulate GPCR function (G. Krause) and design of protein-protein interaction inhibitors (targeting SH3, PDZ, PH or WW domains) (Kühne, G. Krause, Schmieder, Oschkinat).

Topics in the section Structural Biology include, but are not limited, to:
• protein homeostasis
• structure-function relationship of receptors, transporters and channels
• soluble signalling proteins
• molecular imaging based on protein-derived contrast agents

Leibniz-Institut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)