Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Computer Simulations Reveal the Energy Landscape of Ion Channels

Published: Wednesday, May 08, 2013
Last Updated: Wednesday, May 08, 2013
Bookmark and Share
A team of researchers have investigated the opening and closing mechanisms of these channels: for the first time the full energy landscape of such a large protein could be calculated.

The scientists identified a phenylalanine, which plays a key role for the transition between open and closed state. The time consuming calculations were performed using the high performance computer cluster (VSC), which is currently the fastest computer in Austria. Recently, the results were published in PLOS Computational Biology.

Every cell of our body is separated from its environment by a lipid bilayer. In order to maintain their biological function and to transduce signals, special proteins, so called ion channels, are embedded in the membrane. Anna Stary-Weinzinger and Tobias Linder from the University of Vienna and Bert de Groot from the Max Planck Institute of Biophysical Chemistry in Göttingen identified a key amino acid (phenylalanine 114), which plays an essential role for opening and closing of these ion channels.  A conformational change of phenylalanine triggers opening of the channels.

"These proteins are highly selective, they can distinguish between different ions such as sodium, potassium or chloride and allow ion flux rates of up to 100 million ions per seconds", explains Stary-Weinzinger, leader of the research project and postdoc at the Department of Pharmacology and Toxicology of the University of Vienna. "These molecular switches regulate numerous essential body functions such as transduction of nerve signals, regulations of the heart rhythm or release of neurotransmitters. Slight changes in function, caused by replacement of single amino acids, can lead to severe diseases, such as arrhythmias, migraine, diabetes or cancer."

Knowledge of ion channel function provides the basis for better drugs

Ion channels are important drug targets. 10 percent of current pharmaceuticals target ion channels. A detailed understanding of these proteins is therefore essential to develop drugs with improved risk-benefit profiles. An important basis for drug development is a detailed knowledge of the functional mechanisms of these channels. However, there are still many open questions; especially the energy profile and pathway of opening and closure are far from being understood.

Computer simulations visualize ion channel movements

To watch these fascinating proteins at work, molecular dynamics simulations are necessary. Computational extensive calculations were performed with the help of the Vienna Scientific Cluster (VSC), the fastest high performance computer in Austria, a computer cluster operated by the University of Vienna, the Vienna University of Technology and the University of Natural Resources and Applied Life Sciences Vienna. With the help of VSC, the free energy landscape of ion channel gating could be investigated for the first time. The young researchers discovered that the open and closed channel states are separated by two energy barriers of different height.

Phenylalanine triggers conformational changes

Surprisingly, the dynamics of a specific amino acid, phenylalanine 114, are coupled to a first smaller energy barrier. "This side chain acts as molecular switch to release the channel from the closed state", explains Tobias Linder, PhD student from the University of Vienna. After these local changes, the channel undergoes large global rearrangements, leading to a fully open state. This second transition from an intermediate to a fully open pore is accompanied by a large second energy barrier.

This research project is financed by the FWF-doctoral program "Molecular Drug Targets" (MolTag), which is led by Steffen Hering, Head of the Department of Pharmacology and Toxicology of the Faculty of Life Sciences, University of Vienna.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

E. coli Thrive in Patients With Inflammatory Bowel Disease
Researchers have defined a fundamental mechanism through which the bacteria can thrive during IBD flare-ups.
Tuesday, May 12, 2015
Research On Mitochondrial DNA Could Bolster Forensic Investigations
A new grant from the National Institute of Justice (NIJ) will help scientists from Penn State’s Eberly College of Science delve deep into the world of mitochondrial DNA, or mtDNA, used to help solve crime in forensic investigations.
Monday, January 26, 2015
New Grant Tests NGS Tools For Crime Laboratories
National Institute of Justice grant of over $800,000 will test DNA investigative tools utilizing NGS technology.
Friday, January 09, 2015
Altered Milk Protein Can Deliver AIDS Drug to Infants
Binding with an antiretroviral drug promises to greatly improve treatment for infants and young children suffering from HIV/AIDS.
Tuesday, November 11, 2014
Protein Changes Linked to Symptoms of Alzheimer's Disease
Neuroscientists have made a research discovery that helps point the way to potential therapies for memory-related disorders.
Thursday, August 15, 2013
Using Information Technology to Tackle the Root of World Hungar
Scientists are studying what the rest of us don't see--the work going on underneath the ground that enables the growth of healthier crops.
Monday, August 12, 2013
Researchers Discover Protein Changes that Control Whether a Gene Functions
A Penn State-led research team has found that changes to proteins called histones, which are associated with DNA, can control whether or not a gene is allowed to function.
Wednesday, August 07, 2013
Ultraviolet Flashes can Create Vitamin D-Enriched Mushrooms
Quick zaps of ultraviolet light can boost the vitamin D levels in mushrooms in seconds, turning the fungi into an even healthier food, according to Penn State food scientists.
Tuesday, August 06, 2013
Penn State Researchers Part of Award-Winning Africa Research Team
College of Agricultural Sciences scientists are part of a research team that recently won 2013 Africa Collaboration Challenge Prize.
Wednesday, May 29, 2013
Study Suggests Dairy Herd Water Quality Linked to Milk Production
A recently completed study of water supplies on Pennsylvania dairy farms found that about a quarter of those tested had at least one water-quality issue.
Thursday, May 23, 2013
Environmental Law Institute Recognizes Penn State Wetlands Scientist
Robert P. Brooks, a wetlands scientist at Penn State, has received the 2013 National Wetlands Award for Science Research.
Tuesday, May 21, 2013
Probing Question: Do Women Dominate the Field of Forensic Science?
Women going against the stereotype in the booming field of forensic science.
Wednesday, May 08, 2013
Number of Foodborne Illness Cases Largely Unchanged in U.S.
Recently released reports about the frequency of foodborne illness show that the risks have not changed much in recent years, according to an expert in Penn State's College of Agricultural Sciences.
Tuesday, May 07, 2013
Changing Cellulose-Forming Process May Tap Plants' Biofuel Potential
Changing the way a plant forms cellulose may lead to more efficient, less expensive biofuel production, according to Penn State engineers.
Monday, April 29, 2013
Cattle Expert: New Livestock Identification Regulations Not Burdensome
The new livestock identification program recently launched by the federal government should not place a significant burden on producers in Pennsylvania or the East.
Monday, April 29, 2013
Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Study Finds Non-Genetic Cancer Mechanism
Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Researchers Find U.S. Breast Milk is Glyphosate Free
Washington State University scientists have found that glyphosate, the main ingredient in the herbicide Roundup, does not accumulate in mother’s breast milk.
Peering into the Vapors
Research suggests that e-cigarettes are much less harmful than previous studies have indicated.
New Technique for Mining Health-conferring Soy Compounds
A new procedure devised by U.S. Department of Agriculture (USDA) scientists to extract lunasin from soybean seeds could expedite further studies of this peptide for its cancer-fighting potential and other health benefits.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!