Heidelberg researchers simulate processes that trigger muscle movement
Using high-performance computers and quantum mechanical methods, researchers at Heidelberg University have simulated processes that reveal how the “biological spark plug” works in the biomolecular motors of cells. Under the direction of Dr. Stefan Fischer, the investigations focused on the myosin protein, which, among other things, is responsible for muscle movement.
The researchers’ extensive simulations show how the release of energy is initiated in this complex motor. The results of the research conducted at the Interdisciplinary Center for Scientific Computing were published in the journal PNAS.
Biomolecular motors are protein molecules responsible for mechanical movement in cells. These smallest of known motors use the molecule adenosine triphosphate (ATP) as fuel, which all living organisms use as a source of energy for processes that require it. In order to understand how these cell motors use ATP to function, they can be compared to an automobile engine, in which energy is released by burning petrol.
Because petrol does not ignite by itself, energy must be applied to initiate the combustion reaction. This job is done by the spark plug. Energy is not released until the heat energy of the spark is applied to overcome the energy barrier of petrol combustion. According to Stefan Fischer, there are a number of parallels to biomolecular motors. The ATP molecule is stable and like petrol does not release its energy spontaneously. Whereas ATP splits rather than burns, there is also an energy barrier that must be crossed to trigger that splitting, known as hydrolysis.
Dr. Fischer’s research team studied exactly how the trigger mechanism for energy release works in biomolecular motors. “We wanted to find out how the energy stored in the ATP gets released so selectively and precisely timed,” explains the Heidelberg researcher, who heads the Biological Macromolecules working group at the Interdisciplinary Center for Scientific Computing (IWR).
The scientists launched their study of the “biological spark plug” using the biomolecular motor myosin. Myosin is a family of motor proteins that uses ATP, for example to drive muscle movement. The ATP is bound in a sort of “pocket” in the protein. The pocket lowers the energy barrier for splitting the ATP – this process of lowering is known as catalysis – and ensures that the desired chemical reaction ensues and ultimately energy is released. The “catalytic pocket” is the biological equivalent of the spark plug in the combustion engine, according to Dr. Fischer.
The existence of this “biological spark plug” has been known for more than 50 years, but researchers have never been able to fully explain how it works, as Stefan Fischer emphasises: “The reaction takes place in about a trillionth of a second, pushing experimental methods to their limits. This event could not be studied exactly until the computer-assisted methods of scientific computing were applied.”
The scientists first had to identify which of the 6,000 atoms of myosin were essential for catalysis. After comprehensive simulations lasting several years, the researchers identified the role of approximately 200 relevant atoms. Because both the myosin atoms and ATP atoms must move during ATP hydrolysis, the possibilities for movement in three-dimensional space are countless – though only one path leads to the lowest energy barrier. “We had to calculate the paths of all approximately 200 atoms in three dimensions; altogether a problem in 600 dimensions,” says Dr. Fischer.
For their complex calculations, the scientists combined the scientific methods from quantum mechanics with high-performance computers. This allowed them to clarify how the interactions between ATP and myosin are organised in order to lower the energy barrier for splitting ATP. Stefan Fischer explains that the electrostatic charges on the protein atoms are positioned around the ATP in such a way that they modify the electron density of this molecule, making it easier for the ATP fuel to split. “This way we could precisely quantify how much every myosin atom relevant in this process contributed to lowering the energy barrier. Based on these findings we succeeded in clearly formulating the protein’s catalytic strategy.”
The biological spark plug mechanism described by the IWR researchers is not only found in cell motors, but is probably also used in all other protein molecules that use ATP as an energy source, says Dr. Fischer. “Because ATP is the fundamental energy currency of cells, almost all biochemical processes in the body are concerned. In terms of a practical application, our findings may be able to help research on new medications for treating cardiac muscle diseases. Our discoveries may also spur new approaches to treating diseases in which ATP splitting is a part of the biochemistry of the pathological system.”
Farooq Ahmad Kiani and Stefan Fischer: Catalytic Strategy Used By The Myosin Motor To Hydrolyze ATP. PNAS (published online 8 July 8 2014), doi:10.1073/pnas.1401862111
Dr. Stefan Fischer
Interdisciplinary Center for Scientific Computing
Phone: +49 6221 54-8858
Communications and Marketing
Phone: +49 6221 542311
Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences