“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
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine