The brilliance and flux of the synchrotron source BESSY (Berlin) is comparable to the top instruments in the world, allows fast and high-quality X-ray structure determination at very high resolution. The availablity of three beamlines in Berlin provides for unique training opportunities on up-to-date X-ray instrumentation and circumvents the need for PhD students to travel to Grenoble or Hamburg in order to collect their data. The high brilliance of the synchrotron radiation allows to carry out time-resolved infrared experiments (FTIR) i n the mid- and far infrared spectral range, using very small samples (100 µm range). This will enable us to study e.g. conformational changes of membrane proteins upon ligand binding with very small amounts of sample, as arising from site directed mutagenesis. It will also be within the reach of the method to work on small pieces of tissue. Far-infrared coherent IR radiation opens a new and so far unexplored spectral range for the study of membrane proteins. The technique was sucessfully applied to the mechanism of complexation of cations in antibiotics. Circular dichroism spectroscopy (CD) substantially benefits from using the synchrotron beam line of BESSY. The brilliance and the focusability of synchrotron radiation yields a better signal-to-noise ratio in the conventional spectral region above 200 nm. This is of great importance for stopped-flow and continuous-flow CD experiments in order to characterize the kinetics of structural changes in protein folding or misfolding. Conventional sources of electromagnetic radiation like xenon arc lamps are limited to wavelengths of greater than 175 nm. In conventional sources of radiation, the intensity in the spectral region < 175 nm is almost negligible. A substantial gain in structural information is expected exploiting this spectral region.

These facilities which are unique in Germany provide outstanding possibilities for students to get insight in highly sophisticated experimental set-ups, and to carry out their studies at the front-end of research.

NMR facilities (Oschkinat/Reif):

The NMR facilities at the FMP in Berlin-Buch (Oschkinat/Reif) belong to the best equipped laboratories in Germany and provide excellent experimental conditions for solution and MAS solid-state NMR experiments. Solution-state NMR: NMR spectrometers operating at 1H Larmor frequencies of 300 MHz (1), 600 MHz (3), 750 MHz (1) and 900 MHz (time shared with solid-state NMR applications) are equipped with four radiofrequency channels and cryoprobes (3) to run state-of-the art triple resonance experiments. Solid-state NMR: spectrometers operating at 1H larmor frequencies of 400 MHz (1), 600 MHz (1), 700 MHz (1) and 900 MHz (1, shared with solution-state NMR applications).

Ultrastrukturnetzwerk (Spahn):

The Ultrastrukturnetzwerk was founded in 2002 as a cooperative project between the MPIMG (Max-Planck Institut für Molekulare Genetik) and the Charité Universitätsmedizin Berlin and aims for the analysis of supramolecular structure using mass spectrometry and cryo-electronmicroscopy in a proteomics context. The Ultrastrukturnetzwerk is equipped with a Polara G2 300 kV helium cryo-electron microscope manufactured by FEI (Technai F30 with helium-cooled cryo-stage).

EPR-Spectroscopy (Bittl/Herrmann):

The EPR laboratory at the FU Berlin (Dahlem) is equipped with 1 Bruker E680 W-band (95 GHz) CW/pulse EPR spectrometer with pulse ENDOR accessory (4.2–300 K), light access to sample via fiber, 1 Bruker E580 X-/Q-band (9 GHz/ 34 GHz) CW/pulse EPR spectrometer with pulse ELDOR and ENDOR accessory (CW 1.9–300 K, pulse 4.2–300 K), light access to sample, 1 lab-built X-band pulse/transient EPR spectrometer (4.2–300K) light access to sample, 1 lab-built X-band CW-ENDOR spectrometer. In collaboration with Prof. K. Möbius, 1 lab-built W-band CW/pulse EPR/ENDOR spectrometer (120–300 K), light access to sample via fiber and 1 lab-built 360 GHz CW EPR spectrometer (10–300 K), light access to sample via fiber, is available. The EPR laboratory at the HU Berlin (Herrmann) is equipped with two CW EPR spectrometer (X-band) (ECS 106 and EMX 106) including stopped flow equipment.

Thermodynamic measurements (Seckler/Hofmann/Oschkinat):

In addition to determination of the three-dimensional fold of a protein, thermodynamic experiments are essential to properly characterize the interaction between two molecules. Isothermal titration calorimetry (ITC) experiments are usually carried out in order to obtain information on the stoichiometry, the dissociation constant, the free energy, the enthalpy and entropy of binding. State of the art ITC calorimeters are available at the FMP in Berlin-Buch, at the Physical Biochemistry laboratory of Potsdam University, as well as at the IMBP, Charité. Dissociation constants can as well be measured using surface plasmon resonance. 2 Plasmon-resonance spectrometers (Biacore) are available at the FMP. Knowledge of the basic principles of thermodynamics beyond these experiments is a pre-requisite in order to be able to evaluate the obtained data properly.

Electrophysiology (Hegemann):
Electrophysiological measurements allow the determination of voltages and currents across a phospholipid membrane upon interaction with specific effectors (patch-clamp). Expression of the membrane protein of interest in Xenopus oocytes allows the investigation of a functional system in an in vivo like environment. Signalling systems that involve cAMP/cGMP, Ca²⁺, H+, IP3, DAG can be investigated because all these compounds are related to a current influx that is recorded electrically with high signal-to-noise ratio.

Femtosecond laser spectroscopy (Wöste/Siebert):

The molecular dynamics associated with regulation of photoactive protein systems occurring directly after the photo-excitation of the respective cofactor primarily take place within the femtosecond time regime. For the study of these ultrafast processes, the Institute for Experimental Physics at the FU Berlin (Dahlem) is equipped with a state of the arts femtosecond laser laboratory. The laser system is composed of a titanium-sapphire based, broadband femtosecond oscillator and a multi-pass amplification system that provide a general source of sub-50 fs pulses with 1.5 mJ/pulse in the near infrared. This system is coupled to a variety of frequency conversion techniques (parametric frequency mixing and harmonic generation as well as supercontinuum white light) that generate the full spectral rage of femtosecond pulses within the ultraviolet to near infrared. Spatial light modulators further allow for laser pulses with an intricate temporal structure to be constructed that are specifically adapted to the dynamics under investigation. This is achieved through manipulation of amplitude and relative phase of the electric field in the spectral components that composes the laser pulse. Multi-pulse optical techniques such as four-wave mixing will provide an access to complex dynamics in the condensed phase, while the combination of electrospray, tandem mass-spectrometry and ion traps with cryogenic temperature control allows for time-resolved studies in the controlled environment of the gas phase.

Chemically induced dynamic nuclear polarization (Vieth):

The combination of optical and magnetic resonance spectroscopy is exploited at the CIDNP laboratory of the FU-Berlin. The CIDNP technique boosts the sensitivity of NMR and allows one to determine the structural and magnetic resonance properties and the reactivity of radical states of amino acids, nucleotides and peptides, to investigate the intra-molecular electron transfer in peptides and proteins and to compare the structure and intra-molecular mobility of proteins in different states. The group has two 7 T NMR-spectrometers with laser irradiation, one specialized in variable field NMR using field-cycling in the range 0-7 T, the other one for time-resolved CIDNP, and a nanosecond pulsed Stimulated Nuclear Polarization (SNP) device for additional RF pumping of EPR transitions up to 1500 MHz. Also accessible is spin relaxation dispersion over five orders of magnitude of the magnetic field allowing the analysis of motional processes by high resolution NMR.

Thermodynamic characterization of membrane protein folding (Sandro Keller):

Protein–protein, protein–lipid, and lipid–lipid interactions in the anisotropic environment of biological membranes control the folding, oligomerisation, and intramembrane substrate binding of membrane proteins. Highly specific contacts between transmembrane a-helices play a central role in these processes. Unlike in the case of soluble proteins, however, the underlying thermodynamic forces are only poorly understood on a quantitative level. We are aiming at unravelling how avid and how specific such intra- and intermolecular interactions in membrane proteins are and which enthalpic and entropic factors contribute to affinity and specificity. Our lab at the Leibniz Institute of Molecular Pharmacology FMP in Berlin–Buch is equipped with two state-of-the-art isothermal titration calorimeters (ITCs), a combined differential scanning calorimeter (DSC) and pressure perturbation calorimeter (PPC), a UV/vis absorption spectrophotometer, a fluorescence (polarisation) spectrophotometer, and a circular dichroism (CD) spectrophotometer. These microcalorimetric and spectroscopic methods are excellently suited for characterising the thermodynamics of protein folding and protein–protein interactions in membrane-mimetic systems such as artificial lipid vesicles and detergent micelles.