ICS Key Visual

Navigation and service

Protein structure and dynamics

Proteins are the molecular machinery of life. As nanomachines of metabolism, they are in every cell of our body tirelessly active, transport, synthesize, divide and transform substances. The ability of specific proteins to do their job is determined by the sequence of amino acids and their three-dimensional arrangement, but also depends on structural rearrangements dependent on the environmental conditions.

Neutron scattering methods allow examination of structure and dynamics of proteins in D2O buffer solution close to the natural state in the cell. Small angle Neutron scattering (SANS) allows non-destructive determination of the protein shape in solution. In conjunction with SAXS also the hydration layer is accessible.

Neutron Spin Echo Spectroscopy (NSE) is a versatile tool to investigate large-scale movements on the 1 to 200 nanosecond timescale on different length scales with the ability to determine the relaxation time and amplitude of the motions. Quasi-elastic scattering methods as time of flight (TOF) or backscattering (BS) allow the examination on subnanosecond timescale to access motions of amino acid sidechains or hydrogens. Neutron protein crystallography opens up the possibility to locate hydrogen atoms even at atomic resolutions of 2 Å.


Functional collective dynamics of domains

To perform their function structural changes are often important. They reach from atomic reorientation to rearrangements of complete domains that enable to enclose substrates, to release products or to reconfigure domains in complexes. In recent studies we found large scale collective motions of domains in yeast alcohol dehydrogenase and phosphoglycerate kinase [1] (see animation) or the immunoglobulins IgG. The general goal is to identify functional domain motion and characterize timescale and amplitudes by combining SANS and NSE [2].

Intrinsically Unstructured Proteins and Disordered Regions

A large class of proteins has no defined tertiary structure. These proteins have structured parts (or not) connected by disordered regions with high degree of configurational freedom. This class challenges the traditional structure-function paradigm. The IDP's sometimes fold upon binding to an active configuration e.g. in conjunction with other molecules.

Knowledge of dynamics is important to understand the structuring process prior to function, the dynamics of folding or the function as an unstructured protein itself. Two approaches can be used to elucidate the underlying phenomenons. Structured proteins can be unfolded (e.g. by temperature, pressure or chemically) to examine stable unfolded intermediates, transition regions or differences in the different unfolding mechanisms.

A second approach is to observe intrinsically unfolded proteins. As an extreme case a complete unstructured protein should behave as a semiflexible random polymer chain [3]. Structure and dynamics within the unfolding process and for the unfolded protein are influenced by geometrical restrictions as remaining disulfide bonds (see animation of unfolded Ribonuclease A with 4 disulfide bonds), by charges on the amino acid strand or by stiffer regions with eg. a preserved secondary structure.

Local Dynamics

The atoms in a protein show beside the collective domain motions local thermal fluctuations of all atoms on a subnanosecond to picosecond timescale. Underlying motions are bond vibrations, methyl group rotations, motions of the sidechains or of backbone loops at the surface of proteins. These motions differ dependent on the accessible solvent, the local geometry around an atom and the local stabilization e.g. due to secondary structure and on the general topology of the protein.

For alcohol dehydrogenase, a large tetrameric protein, we found a diffusive motion slower than solvent water and confined to about 0.7 nm, which we attribute to dangling solvent-exposed side groups at the surface of the protein [4]. The general aim is to examine where the dynamics has its largest contributions dependent on the topology from globular proteins to unfolded proteins.


Protonation States of Proteins

Neutron crystallography locates the hydrogen atom positions in protein crystals, which are not properly seen by X-rays. The Bragg-reflections from a sperm whale myoglobin crystal measured with the BioDiff instrument, a dedicated instrument for neutron protein crystallography at MLZ in Garching together with the resulting protein structure is shown below. The additional information gained with neutron protein crystallography is for example the identification of unusual hydrogen bonds, the protonation state of amino acid side chains and the solvent structure around the protein [5].

In order to grow the large protein crystals that are required for this method detailed knowledge on the phase diagram of the corresponding protein is required. Also, a better understanding of the processes involved in crystallization is needed. Among other techniques, neutron small angle scattering in combination with in-situ dynamic light scattering and quasi-in-situ static light scattering is especially well-suited to follow the crystallization process in real time.

Dedicated effort is put into the development of such techniques to provide more information on the crystal nucleation and growth process.


[1] R. Inoue, R. Biehl, T. Rosenkranz, J. Fitter, M. Monkenbusch, A. Radulescu, B. Farago, and D. Richter, Biophys J 99, 2309 (2010).

[2] R. Biehl and D. Richter, J. Phys. Condens. Matter 26, 503103 (2014).

[3] A. M. Stadler, L. Stingaciu, A. Radulescu, O. Holderer, M. Monkenbusch, R. Biehl, and D. Richter, J. Am. Chem. Soc. 136, 6987 (2014).

[4] M. Monkenbusch, A. Stadler, R. Biehl, J. Ollivier, M. Zamponi, and D. Richter, J. Chem. Phys. 143, 075101 (2015).

[5] C.M. Casadei, A. Gumiero, C.L. Metcalfe, E.J. Murphy, J. Basran, M.G. Concilio, S.C.M. Teixeira, T.E. Schrader, A.J. Fielding, A. Ostremann, M.O. Blakely, E.L. Raven, P.C.E. Moody, Science 345, 193-197 (2014)











Dear visitor,

To make our website suit your needs even more and to give it a more appealing design, we would like you to answer a few short questions.

Answering these questions will take approx. 10 min.

Start now Close window

Thank you for your support!


In case you have already taken part in our survey or in case you have no time to take part now, you can simply close the window by clicking "close".

If you have any questions on the survey, please do not hesitate to contact: webumfrage@fz-juelich.de.


Your Team at Forschungszentrum Jülich


Note: Forschungszentrum Jülich works with the market research institute SKOPOS to anonymously conduct and analyze the survey. SKOPOS complies with the statutory requirements on data protection as well as with the regulations of ADM (Arbeitskreis Deutscher Markt- und Sozialforschungsinstitute e.V.) and ESOMAR (Europäische Gesellschaft für Meinungs- und Marketingforschung). Your data will not be forwarded to third parties.