Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rensselaer Researchers Create Accurate Computer Model of RNA Tetraloop

17.09.2013
A computational model developed by researchers at Rensselaer Polytechnic Institute is the first to accurately simulate the complex twists of a short sequence of RNA as it folds into a critical hairpin structure known as a “tetraloop.”

The research, published today in Proceedings of the National Academy of Sciences, is a glimpse into RNA, found in all life on Earth, and could advance a variety of research areas, including the search for new antibiotics and cures for protein-related diseases.


A simulation of the GCAA tetraloop folding: The color code is red=guanine, green=cytosine, and yellow=adenine, and dotted white lines are hydrogen bonds. There is a cyan overlay in the last 5 seconds indicating the experimentally determined structure.
http://www.youtube.com/watch?feature=player_embedded&v=Xc8clJzvRWc

Existing computational models, based on DNA rather than RNA, do not achieve the atomic level accuracy of the new model, said Angel Garcia, head of the Department of Physics, Applied Physics, and Astronomy within the School of Science at Rensselaer, and senior constellation chaired professor in the Biocomputation and Bioinformatics Constellation, who co-wrote the paper with Alan Chen, a post-doctoral fellow at Rensselaer. The new model Garcia and Chen created can simulate the folding of three known versions of a tetraloop, accurate to within one ten-billionth of a meter.

RNA is involved in many biological functions, such as building proteins, coding and decoding genes, and cellular regulation. RNA molecules are composed of strings of four different “bases” —cytosine, guanine, adenine, and uracil—mounted on a sugar-phosphate backbone. Once the sequence is assembled, the individual bases interact with their neighbors, twisting and swinging on the hinged chemical bonds that connect them to the backbone. When the process is complete, the RNA has folded into its “tertiary” structure, which influences its function. Although researchers can easily alter the sequence of molecules, without accurate computer modeling there they cannot easily see the tertiary structure of their creation.

“Right now, it takes people from molecular biologists, to virologists, to cell biologists, thousands of dollars and years of study to see the structure of an RNA they have made, altered, or are studying,” said Chen. “There are a lot of researchers working on the RNA in viruses and how it attacks the cell, and, while they’re easily able to alter the sequence, they’re essentially working without ever seeing the effects of their changes in molecular detail. Because of this, there’s a lot of trial and error, and our work aimed at helping that.”

Garcia and Chen said that, unlike DNA, which typically twists two strands of bases into a classic double-helix, RNA is single-stranded and folds onto itself, forming many unusual structures. A tetraloop is a small section of single-stranded RNA that is looped into the shape of a hairpin, the curve of which is formed by four bases. Even the sequence of bases in a tetraloop is unusual, violating a standard arrangement described by groundbreaking DNA researchers James Watson and Francis Crick.

To create an effective computational model, Garcia and Chen had to match the unique “recipe” of twisting and swinging proscribed by the interactions between the bases.

“Imagine if you try to produce a recipe of Mario Batali,” said Garcia, referring to a popular chef. “I tell you it has water, salt, fish, and pasta—go produce his recipe. The problem is, you don’t know how much of each, and in what order.”

Instead of a recipe of food ingredients, Garcia and Chen created a computational recipe for the interactions of the bases in the sequence of a tetraloop.

“The problem is one of balancing different forces. It’s the actions between the bases as they stack on top of each other, the interactions of the bases with water, the rotation of the bases relative to a sugar. Those are things that change the balance,” said Garcia.

Garcia said tetraloops are an important area of study because they appear in all organisms, particularly in ribosomes, which manufacture proteins for living cells. Statistically, there could be as many as 256 possible sequences of those four bases, but only three sequences actually appear in tetraloops. Once formed, they are highly stable, outlasting other structures when subjected to the destructive force of increasing heat.

“Tetraloops are sequences which are highly conserved throughout evolution; you find them everywhere, from bacteria to humans,” said Garcia. “From one organism to another, many things can change, but when tetraloops change, they change from one sequence of four bases to one of the other three. They stack against each other and they are hyperstable. And there is a reason for them to be arranged the way they are.”

The paper, titled “High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations,” appears in the September 16 online early edition of PNAS, and will be published in the September 20 print edition.

Contact: Mary L. Martialay
Phone: (518) 276-2146
E-mail: martim12@rpi.edu

Mary Martialay | EurekAlert!
Further information:
http://www.rpi.edu

More articles from Physics and Astronomy:

nachricht A 100-year-old physics problem has been solved at EPFL
23.06.2017 | Ecole Polytechnique Fédérale de Lausanne

nachricht Quantum thermometer or optical refrigerator?
23.06.2017 | National Institute of Standards and Technology (NIST)

All articles from Physics and Astronomy >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>