Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein energy profiles offer clues about amyloids

05.10.2004


Rice study probes basic science related to Alzheimer’s, other diseases

Patients suffering from diseases as varied as Type II diabetes, Alzheimer’s, Parkinson’s and dozens of lesser known maladies have one thing in common: they suffer from a large build up of amyloids, tissue that’s created when millions upon millions of misfolded proteins stick together and form a mass that the body can’t get rid of on its own. Doctors don’t yet understand whether amyloids cause disease or result from it, but the fact that they are present in very different diseases affecting millions of people points to the need for improved understanding of the basic processes of protein folding, one of the most complicated and least understood of all biological phenomena.

Research appearing in the Oct. 8 issue of the Journal of Molecular Biology, describes a new technique that may help scientists predict which proteins are prone to misfold and at what point the folding process is likely to break down. The research could support efforts to find the causes for diseases involving amyloids, and it could prove useful for researchers studying proteins involved in even more prevalent diseases like cancer and heart disease.



"We know now that most diseases involve proteins going wrong in one of two ways," said lead researcher Cecilia Clementi, assistant professor of chemistry at Rice University. "In the first, proteins don’t function correctly because they fold into the wrong shape. This is something we see in sickle-cell anemia, for instance, because of genetic flaws that cause the amino acid sequence to be incorrectly synthesized.

"The second way proteins go wrong is by not folding at all, which is what we find in diseases involving amyloids. In these situations, the misfolded proteins assemble together into macroscopic aggregates."

All the basic functions of life are carried out by proteins, and the DNA in each of our cells contains the blueprints for all the proteins we need. Every protein has a characteristic shape, and it folds itself into that shape very soon -- generally in less than a second -- after it is made. To carry out their tasks, proteins interact with one another, bind with some molecules, cleave others into pieces and fuse other molecules together.

Since the function of a protein is often based upon specific chemical interactions -- enzymes, for instance, are proteins that make or disrupt chemical bonds in other molecules -- individual atoms of a protein must be aligned just so if they are to function properly. Consequently, there is a direct relationship between a protein’s shape and its function.

The study of amyloids is complicated by the fact that the shape of very few proteins is known, the mechanics of protein folding are a mystery, and protein folding is incredibly complex; even the fastest supercomputer in the world would take decades to simulate all of the chemical interactions that take place when a single protein folds itself into its characteristic shape.

Despite this mystery and complexity, Clementi and colleagues believe they are creating a statistical method that will help scientists predict which proteins are prone to misfold.

"In designing a computer model for protein folding, you can’t take everything into account because there are too many variables," said Vijay Pande, assistant professor chemistry and of structural biology at Stanford University and founder of the Folding@Home distributed computing project. "By designing simplified models that retain the essential physical and chemical features of protein dynamics, Clementi’s team is making excellent progress in quantitative prediction -- work that’s highly complimentary to the detailed simulations we’re creating through Folding@Home."

Basic thermodynamics dictates that the entire process of protein folding can be seen as the systematic progression of the unfolded protein into its lowest possible free energy state. To identify whether a protein is a candidate for misfolding, Clementi has devised a dynamic interplay between theory and experiment -- with each informing the other as an experiment is carried out -- to construct a profile of the energy states a protein progresses through while it folds.

When this energy profile is plotted on a multidimensional graph, Clementi and her colleagues study the image like a mountain range, looking for low-lying valleys -- reduced energy states where the protein is most likely to become sidetracked before it can finish folding into its proper shape.

Ultimately, Clementi hopes the technique will be refined and used to catalog the folding energies of proteins that have already been implicated in specific diseases. She believes the profiles could offer new clues to doctors and drug companies about which proteins are good candidates for drug therapy.

Clementi co-authored the latest study with graduate student Silvina Matysiak. Two other graduate students in Clementi’s group, Payel Das and Alexei Tcherniak, and undergraduate student Yoav Kallus, are working with Clementi and Matysiak to test and improve the technique for practical applications.

Jade Boyd | EurekAlert!
Further information:
http://www.rice.edu

More articles from Life Sciences:

nachricht New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences

nachricht The main switch
21.11.2017 | 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: Nanoparticles help with malaria diagnosis – new rapid test in development

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....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

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...

Im Focus: Visual intelligence is not the same as IQ

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...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

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....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>