Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Computer Simulation Shows How Fibrils " Proteins That Cluster in Diseases " Form

23.11.2004


The NC State simulation shows randomly placed peptides forming a fibril.


To get a better look at how proteins gather into clusters called amyloid fibrils – which are associated with important human diseases such as Alzheimer’s, Parkinson’s and the so-called prion diseases like Mad Cow – researchers at North Carolina State University decided to make movies.

Dr. Carol Hall, Alcoa Professor of chemical engineering at NC State and Hung D. Nguyen, a graduate student in Hall’s lab, used a computer simulation technique, discontinuous molecular dynamics, to visualize the meanderings of small proteins called peptides. Movies of the simulation show that 96 randomly placed peptides spontaneously aggregate into what Hall calls a “sandwich” of layered protein sheets, similar to the amyloid fibrils discovered in diseased people and animals. Hall says that understanding how fibrils form in human or animal organs may lead to discoveries of how to slow or halt fibril formation.

The research was published in the Nov. 16 edition of Proceedings of the National Academy of Sciences. It is not known whether fibrils cause Alzheimer’s, Parkinson’s and the other so-called amyloid diseases, or whether they are just associated symptoms. In any event, the fibrils form plaques in human and animal organs, often the brain. Although it’s not clear if these plaques cause memory loss in Alzheimer’s patients, for instance, scientists are interested in finding out the mechanisms behind the formation of fibrils.



“All of these diseases – Alzheimer’s, Parkinson’s, ALS, Huntington’s – have the same unusual phenomena. Proteins – completely different proteins in each disease – assemble into ordered aggregates, amyloid fibrils, so that a vital organ, usually the brain, is crisscrossed by these structures,” Hall said. “This tells us that the problem has something to do with the general nature of proteins rather than with the specifics of the particular disease-associated proteins.”

Besides studying fibrils in the test tube, researchers would like to make computer models to view fibril formation. This is not possible using the traditional atomic-level protein folding simulation techniques – which follow the motions of every atom on every protein – because fibril formation takes a long time.

So Hall and Nguyen developed a less-detailed model of protein geometry and energetics and applied it to a relatively simple protein, polyalanine, which had been found to form fibrils in test tubes. With this approach, the NC State researchers were able to watch spontaneous fibril formation in about 60 hours on a fast computer. That’s much quicker than atomic-level simulations.

In the simulation movie, 12 to 96 peptides were initially scattered randomly across the computer screen. When set into motion, the researchers first saw groups of two to five proteins coming together and falling apart and eventually forming amorphous clumps that twist around each other, like a rope. These twisted structures began coming together, like the ingredients in a sandwich, layered above and below each other. In the end, the simulation showed a fibril-like structure with only a few outlying peptides refusing to aggregate.

Hall says her method of reducing the level of detail in her protein model just to the point where the key features that drive fibril formation remain and other features are neglected allows her to get a broad molecular-level picture of the fibril formation process.

Hall’s work is sponsored by the National Institutes of Health. She has recently been funded to attempt computer simulations of fibril formation by beta amyloids, the peptides that aggregate in Alzheimer’s disease.

Dr. Carol Hall | EurekAlert!
Further information:
http://www.ncsu.edu

More articles from Life Sciences:

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

nachricht How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>