“Imagine an inflated balloon attached to a pump, but much, much smaller. By pinching off the neck of the balloon with a noose, it is detached from the pump and is able to move about freely.” The description is an approximation of one of the molecular processes looked at by mathematician Dr. Frank Noe as part of MATHEON’S ‘A19, Modelling and Optimisation of Functional Molecules’ project. Specifically, the molecular structure and mechanism of dynamin.
In the case of dynamin, the precise mechanism of action can be visualised in individual steps
Dynamin is a protein and the ‘noose’ which detaches the balloon from the pump. The vesicle (the scientific name for the balloon) has to be detached to allow it to perform its role as a vesicle for transporting messenger substances and nutrients into the cell. Substances which need to be transported into the cell first accumulate in a vesicle formed by invagination from the surface of the cell. The dynamin molecule then attaches to the neck of the vesicle and forms a spiral around it. It then severs the neck of the vesicle. The vesicle is now free to transport nutrients into the cell.
Whilst scientists have long known about the process, the molecular details of how dynamin works were until now unknown. A group of researchers at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin has now managed to obtain snapshots of the detailed molecular structure and, with the help of mathematical research carried out by Frank Noe and his team at MATHEON, been able to breathe life into these static structures.
Simulating this molecular process is extremely difficult. “A simulation encompasses 250,000 particles and each iteration of the calculation takes around 1 second, even on a mainframe. To directly simulate this process, we would have to perform millions of iterations. That would take decades – scission within the cell takes just milliseconds.” With the help of mathematical methods developed at MATHEON, it was possible to divide the scission process up into many smaller, more manageable simulations.
In the case of dynamin, this allowed the precise mechanism of action to be visualised in individual steps. It turns out that the molecule operates via a specific pathway. “We were able to identify three primary states of the molecule,” explains the mathematician, describing the process as follows, “Initially, dynamin molecules attach to the neck of the vesicle individually, before linking up to form between one and a half and two tight turns around the neck of the vesicle. This structure then expands like a spring and rotates in on itself. The result is that the semi-fluid material making up the neck of the vesicle is more or less ripped apart. “
Understanding this process is important for medical science, as it represents a point of attack for fighting poisons and disease. “Many neurotoxins, for example, act at this point, thereby blocking nerve function,” explains Frank Noe. Degenerative neurological diseases such as Parkinson’s also affect the uptake of vesicles by nerve cells. “If we can obtain a better understanding of the mechanism of dynamin, we may be able to find new approaches to early diagnosis or treatments,” says Dr. Noe.
Collaboration between doctors, structural biologists and mathematicians in this area is set to continue. “The mathematical research being carried out within the MATHEON project will continue to make an important contribution to producing further useful insights,” explains Frank Noe.The study has been published in the journal ‘Nature’, issue 477, page 556. Further information on the study can be found at
Rudolf Kellermann | idw
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy