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 Progress in Super-Resolution Microscopy
17.12.2018 | Julius-Maximilians-Universität Würzburg

nachricht Communication between neural networks
17.12.2018 | 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: Data storage using individual molecules

Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.

Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

When a fish becomes fluid

17.12.2018 | Studies and Analyses

Progress in Super-Resolution Microscopy

17.12.2018 | Life Sciences

How electric heating could save CO2 emissions

17.12.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>