New substance library to accelerate the search for active compounds

In order to accelerate the systematic development of drugs, the MX team at the Helmholtz-Zentrum Berlin (HZB) and the Drug Design Group at the University of Marburg have established a new substance library. It consists of 1103 organic molecules that could be used as building blocks for new drugs. The MX team has now validated this library in collaboration with the FragMAX group at MAX IV. The substance library of the HZB is available for research worldwide and also plays a role in the search for substances active against SARS-CoV-2.

For drugs to be effective, they usually have to dock to proteins in the organism. Like a key in a lock, part of the drug molecule must fit into recesses or cavities of the target protein. For several years now, the team of the Macromolecular Crystallography Department (MX) at HZB headed by Dr. Manfred Weiss together with the Drug Design Group headed by Prof. Gerhard Klebe (University of Marburg) has therefore been working on building up what are known as fragment libraries. These consist of small organic molecules (fragments) with which the functionally important cavities on the surface of proteins can be probed and mapped. Protein crystals are saturated with the fragments and then analysed using powerful X-ray light. This allows three-dimensional structural information to be obtained at levels of atomic resolution. Among other things, it is possible to find out how well a specific molecule fragment docks to the target protein. The development of these substance libraries took place as part of the joint Frag4Lead research project and was funded by the German Federal Ministry of Education and Research (BMBF).

Read more on the BESSY II website

Image : For the study, the enzyme endothiapepsin (grey) was combined with molecules from the fragment library. The analysis shows that numerous substances are able to dock to the enzyme (blue and orange molecules). Every substance found is a potential starting point for the development of larger molecules. 

Credit: Wollenhaupt/HZB

Insights into the visual perception of plants

Plants use light not only for photosynthesis. Although the plant cell does not have eyes, it can still perceive light and thus its environment. Phytochromes, certain turquoise proteins, play the central role in this process. How exactly they function is still unclear. Now a team led by plant physiologist Jon Hughes (Justus Liebig University Gießen) has been able to decipher the three-dimensional architecture of various plant phytochrome molecules at BESSY II. Their results demonstrate how light alters the structure of the phytochrome so that the cell transmits a signal to control the development of the plant accordingly.

Plants use light to live, via a process called photosynthesis. Yet, they do use light also by so called phytochromes – special molecules that give plants a kind of sight and can thus control the biochemistry of the cell and the development of the plant. It is now known that phytochromes regulate almost a quarter of the plant genome.

Read more on the BESSY II (at HZB) website

Image : Inside the 3D-structure of a phytochrome a bilin pigment absorbs the photon and rotates, which triggers a signal

Credit: Jon Hughes

New cryo-EM Collaboration

UK set to be global leader in providing large-scale industrial access to Cryo-EM for drug discovery thanks to new collaboration.


Thermo Fisher Scientific and Diamond Light Source are creating a step change for life sciences sector, a one-stop shop for structural biology and one of largest cryo-EM sites in the world.
An agreement to launch a new cryo-EM capability for use in the life sciences industry sector by Thermo Fisher Scientific, one of the world leaders in high-end scientific instrumentation, and Diamond Light Source, the UK’s national synchrotron and one of the most advanced scientific facilities in the world, was announced today ahead of the official opening of the new national electron bio-imaging centre (eBIC) which will be held at Diamond on September 12th 2018.

This announcement confirms Diamond as one of the major global cryo-EM sites embedded with an abundance of complementary synchrotron-based techniques, and thereby, provides the life sciences sector with an offer not available anywhere else in the world.

Professor Dave Stuart, Life Sciences Director at Diamond and MRC Professor of Structural Biology at the University of Oxford, Department of Clinical Medicine, says, “Access to 21st century scientific tools to push the boundaries of scientific research is essential for both academia and industry, and what we have created here at Diamond is truly unique in the world in terms of size and scale. The new centre offers the opportunity for almost real-time physiology, capturing proteins in action at cryo-temperatures by flash-freezing them at various stages. What Diamond has created with eBIC is an integrated facility for structural biology, which will accelerate R&D for both industry and academic users. The additional advanced instruments made available by Thermo Fisher will position the UK as a global leader in providing large-scale industrial access to cryo-EM for drug discovery research. Our new collaboration provides a step change in our offer for industry users and helps ensure that R&D remains in the UK.”

>Read more on the Diamond Light Source website

Image: Close up sample loading Krios I.

Video presentation of thesis at NanoMAX

In April 2018, Karolis Parfeniukas (image) defended the first thesis to be fully completed at one of the new MAXIV beamlines called NanoMAX Here’s an interview with Karolis about this project making zone plates to improve focusing of the X-ray beam. Thesis from KTH university, Royal Institute of Technology in Stockholm. PLease watch here the presentation of his research at MAX IV Laboratory:

>Read more here about MAX IV Laboratory

MicroMAX, a new beamline for life science

The Novo Nordisk Foundation has generously decided to fund the construction and operation of a new beamline at the MAX IV Laboratory called MicroMAX with 255 million DKK.

MicroMAX has been proposed by the Swedish and Danish research community and will depend on close collaboration with user groups in developing the methods that will be used at MicroMAX. The group of Professor Richard Neutze at the University of Gothenburg has pioneered the research in this area.

– Looking back, I note that in November 2006 MicroMAX was priority #2 in the Swedish Research Council evaluation of the proposal to construct MAX IV Laboratory, says Richard Neutze. Now we have a construction and build-up of the beamline also stretching more than a decade. For the MAX IV project as a whole this is a hugely important decision, to get this level of support from a Danish Foundation. I believe that MicroMAX will be one of the major flagship projects for MAX IV Laboratory. Now we just have to build it, operate it and do some great science…. the fun bit!

>Read more on the MAX IV website