Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Free-energy theory borne out in large-scale protein folding

05.10.2005


Marriage of theory, experiment is first for multi-domain protein folding



In unprecedented new research, scientists at Rice University have combined theory and experiment for the first time to both predict theoretically and verify experimentally the protein-folding dynamics of a large, complex protein. The interdisciplinary research appears this week in two back-to-back papers in the Proceedings of the National Academy of Sciences.

"Researchers have successfully combined computer modeling and experimental results in folding studies for small proteins, but this is the first effective combination for a large, multi-domain protein," said study co-author Kathleen Matthews, Dean of the Wiess School of Natural Sciences and Stewart Memorial Professor of Biochemistry. "Pioneering efforts were required to establish comparable experimental and theoretical data, and the method worked remarkably well. We expect others to adopt it in their own studies."


Proteins are the workhorses of biology. At any given time, each cell in our bodies contains 10,000 or more of them. Each of these proteins is a chain of amino acids strung end-to-end like beads in necklace. For longer proteins, the chain can contain hundreds of amino acids.

Thanks to modern genomics, scientists can use DNA to decipher the amino acid sequence in a protein. But knowing the sequence gives no clue to the protein’s function, because function is inextricably tied to shape, and every protein self-assembles into its characteristic shape within seconds of being created.

"The folded, functional form of the protein is what really matters, and our interest is in creating a folding roadmap of sorts, a plot of the thermodynamic route that the protein follows as it moves toward equilibrium," said co-author Cecilia Clementi, the Norman Hackerman-Welch Young Investigator Assistant Professor of Chemistry.

The Rice research team included Clementi, Clementi’s graduate student Payel Das, experimentalist Pernilla Wittung-Stafshede, associate professor of biochemistry and cell biology, Matthews and graduate student Corey Wilson of biochemistry and cell biology.

"We know that misfolded proteins play a key but mysterious role in Alzheimer’s, Parkinson’s, diabetes and a host of other diseases, so mapping the normal route a protein takes – and finding the off-ramps that might lead to misfolding – are vitally important," Wittung-Stafshede said.

Rice’s studies were carried out on monomeric lactose repressor protein, or MLAc, a variant of the protein used by E. coli to regulate expression of the proteins that transport and metabolize lactose. MLAc contains about 360 amino acids.

While scientists know proteins containing 100 or fewer amino acids fold in a very cooperative (all-or-none) fashion, it is believed that larger proteins fold through the formation of partially folded intermediate structures before settling into their final state.

Simulating large-scale protein folding is too complex for even the most powerful supercomputer. In developing a theoretical approach that allows studying protein folding on a computer, Clementi and Das relied on the techniques of statistical mechanics, building up an overall picture of MLAc folding based upon statistical approximations of molecular events.

On the experimental side, Wittung-Stafshede, Matthews and Wilson prepared samples of MLAc and added urea to cause them to unfold. The team then injected water into the solution very fast, diluting the mixture and causing the proteins to fold. Using spectroscopy, they captured fluorescence and ultraviolet polarization patterns given off by the proteins as they folded.

"The novelty of this work is the direct and quantitative comparison of the time-dependent simulation data with the experimental measurements from circular dichroism and tryptophan fluorescence," Das said. "The excellent agreement between experiment and theory illustrates that the existence of a well-defined "folding route", at least for large proteins, can be predicted within the framework of free-energy landscape theory. This has been a very controversial issue in the field of protein folding."

Study co-authors also included Giovanni Fossati, assistant professor of physics and astronomy, who helped the team analyze and interpret the simulation data.

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

More articles from Interdisciplinary Research:

nachricht New dental implant with built-in reservoir reduces risk of infections
18.01.2017 | KU Leuven

nachricht Many muons: Imaging the underground with help from the cosmos
19.12.2016 | DOE/Pacific Northwest National Laboratory

All articles from Interdisciplinary Research >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>