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

Computer Modeling Shows Crucial Function of Water Molecules in Proteins

Published: Wednesday, July 31, 2013
Last Updated: Wednesday, July 31, 2013
Bookmark and Share
Scientists used molecular simulations that modeled a potassium channel and its immediate cellular environment, atom for atom.

UChicago scientists have discovered that just 12 molecules of water cause the long post-activation recovery period required by such ion channels before they can function again.

The research has revealed a new mechanism in the function of a nearly universal biological structure that will have broad implications, ranging from fundamental biology to the design of pharmaceuticals.

“Our research clarifies the nature of this previously mysterious inactivation state. This gives us better understanding of fundamental biology and should improve the rational design of drugs, which often target the inactivated state of channels,” said Benoît Roux, professor of biochemistry and molecular biology, whose team’s findings were published online July 28 in Nature.

Potassium channels, present in the cells of virtually all living organisms, are core components in bioelectricity generation and cellular communication. Required for functions such as neural firing and muscle contraction, they serve as common targets in pharmaceutical development.

These proteins act as a gated tunnel through the cell membrane, controlling the flow of small ions into and out of cells. After being activated by an external signal, potassium channels open to allow ions through. Soon after, however, they close, entering an inactive state and are unable to respond to stimuli for 10 to up to 20 seconds.

The cause of this long recovery period, which is enormously slow by molecular standards, has remained a mystery, as structural changes in the protein are known to be almost negligible between the active and inactivated states—differing by a distance equivalent to the diameter of a single carbon atom.

To shed light on this phenomenon, Roux and his team used supercomputers to simulate the movement and behavior of every individual atom in the potassium channel and its immediate environment. After computations corresponding to millions of core-hours, the team discovered that just 12 water molecules were responsible for the slow recovery of these channels.

They found that when the potassium channel is open, water molecules quickly bind to tiny cavities within the protein structure, where they block the channel in a state that prevents the passage of ions. The water molecules are released slowly only after the external stimulus has been removed, allowing the channel to be ready for activation again. This computer simulation-based finding was then confirmed through osmolarity experiments in the laboratory.

“Observing this was a complete surprise, but it made a lot of sense in retrospect,” Roux said. “Better understanding of this ubiquitous biological system will change how people think about inactivation and recovery of these channels, and has the potential to someday impact human health.”

The work was supported by grants from the National Institutes of Health. Computation resources were provided by Oak Ridge National Laboratory, the National Resource for Biomedical Supercomputing and the Pittsburgh Supercomputing Center.


Further Information

Join For Free

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 3,300+ scientific posters on ePosters
  • More Than 4,900+ 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

New Technique Targets Ataxia Gene
Scientists selectively turn off the disease-causing portion of a gene that causes a severe form of ataxia.
Thursday, July 14, 2016
Organ Behaviour Manipulation Possible with New Injectable
Scientists develop injectable that could be used to stimulate nerve cells and manipulate muscle and organ behaviour.
Friday, July 08, 2016
New Microbiome Center to Merge Expertise of UChicago, MBL and Argonne
Researchers to study world of microbes across environments.
Wednesday, May 18, 2016
AbbVie, University of Chicago Collaborate
The University of Chicago and AbbVie have entered into a five-year collaboration agreement designed to improve the pace of discovery and advance medical research in oncology at both organizations.
Thursday, April 21, 2016
New Code for Control of Gene Expression
A new cellular signal discovered by a team of scientists at the University of Chicago and Tel Aviv University provides a promising new lever in the control of gene expression.
Thursday, February 18, 2016
Bacterial Circadian Clocks Set by Metabolism, Not Light
New study finds that metabolism is the primary driver of the circadian rhythm.
Monday, December 14, 2015
New Nanomanufacturing Technique Advances Imaging, Biosensing Technology
Researchers invent a novel way to build nanolenses in large arrays using a combination of chemical and lithographic techniques.
Thursday, December 10, 2015
Enormous Genetic Variation May Shield Tumors from Treatment
Debate over Darwinian selection vs. random mutations emerges at the tumor level.
Wednesday, November 11, 2015
Gut Bacteria Can Dramatically Amplify Cancer Immunotherapy
Manipulating microbes maximizes tumor immunity in mice.
Monday, November 09, 2015
Protein Aggregation After Heat Shock Is An Organized, Reversible Response
New study finds protein aggregation after heat exposure is a reversible cellular process, not unrecoverable damage from misfolding.
Friday, September 11, 2015
New Form of DNA Modification May Carry Inheritable Information
Scientists have described the surprising discovery and function of a new DNA modification in insects, worms and algae.
Friday, May 08, 2015
Shape-Shifting Molecule Tricks Viruses Into Mutating Themselves To Death
Study uses two-dimensional infrared spectroscopy to help distinguish between normal and shape-shifted structures.
Thursday, April 16, 2015
Drug-Development Grants Focus On Sleep Apnea, Asthma Research
NIH grants awarded to two University of Chicago research teams will help to develop novel treatments for sleep apnea and asthma.
Tuesday, January 27, 2015
Gut Bacteria that Protect Against Food Allergies Identified
Common gut bacteria prevent sensitization to allergens in a mouse model for peanut allergy, paving the way for probiotic therapies to treat food allergies.
Wednesday, August 27, 2014
Researchers Identify ‘Fat Gene’ Associated with Obesity
Mutations within the gene FTO have been implicated as the strongest genetic determinant of obesity risk in humans, but the mechanism behind this link remained unknown.
Monday, March 17, 2014
Scientific News
Breakthrough Flu Vaccine Inhibited by Pre-existing Antibodies
Universal truths – how existing antibodies are sabotaging the most promising new human flu vaccines.
Gene Therapy for Metabolic Liver Diseases
Researchers have tested gene therapy in pigs from hereditary tyrosinemia type 1, with corrected liver cells being transplanted into the diseased liver.
Zika Vaccine Candidates Show Promise
Two experimental vaccines have shown promise against a major viral strain responsible for the Brazilian Zika outbreak.
New Medication Shows Promise Against Liver Fibrosis in Animal Studies
Liver fibrosis is a gradual scarring of the liver that puts people at risk for progressive liver disease and liver failure.
Raw Eggs Deemed Safe to Eat
A report published today by the Advisory Committee on the Microbiological Safety of Food (ACMSF) into egg safety has shown a major reduction in the risk from salmonella in UK eggs.
Monitoring TTX Toxin in Shellfish
In a number of small studies, mussels and oysters from the eastern and northern part of the Oosterschelde in Holland were found to contain tetrodotoxin (TTX).
Gene Terapy for Muscle Wasting Developed
New gene therapy could save millions of people suffering from muscle wasting disease.
NIH Begins Yellow Fever Vaccine Trial
NIH has initiated an early-stage clinical trial of a vaccine to protect against yellow fever.
Gene-Editing 'Toolbox' Targets Multiple Genes Simultaneously
Researchers have designed a system that modifies, or edits, multiple genes in a genome at once while minimising unintentional effects.
Detecting Alzheimer's with Smell Test
Odour identification test may offer low-cost alternative for predicting cognitive decline and detecting early-stage Alzheimer’s disease.
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!