Featured Research

from universities, journals, and other organizations

Key Molecular Basis Of Cystic Fibrosis Identified Through Computer Simulations

Date:
March 3, 2008
Source:
Public Library of Science
Summary:
Researchers have identified a key molecular mechanism that may account for the development of cystic fibrosis, which about 1 in 3,000 children are born with in the US every year. The findings add new knowledge to understanding the development of this disease and may also point the way to new corrective treatments.

Researchers from the University of North Carolina at Chapel Hill have identified a key molecular mechanism that may account for the development of cystic fibrosis, which about 1 in 3000 children are born with in the US every year. The findings add new knowledge to understanding the development of this disease and may also point the way to new corrective treatments.

Cystic fibrosis (CF) is a fatal disease caused by a defective gene that produces a misshapen form of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. People with cystic fibrosis do not have enough CFTR for their cells to work normally because their bodies quickly destroy the mutant protein. The deletion of this protein specifically occurs in a major domain of CFTR called NBD1. Earlier experimental studies have shown that the mutant NBD1 has an increased tendency to misfold, resulting in the premature degradation of CFTR.

In CF, the molecular basis of this increased misfolding tendency has remained elusive, said team leader Nikolay Dokholyan. "Understanding molecular etiology of the disease is a key step to developing pharmaceutical strategies to fight this disease," Dokholyan said.

Using molecular dynamics simulations, the researchers performed extensive simulations of how normal and mutant NBD1 folded. Molecular dynamics simulation is akin to a "virtual experiment" wherein atoms and molecules are allowed to evolve according to known physical laws. Using computers, this virtual experiment allows researchers to view how atoms actually move. These simulations, when applied to the NBD1 protein, showed that the disease-causing mutant exhibits a higher misfolding tendency.

More importantly, by comparing the structures of the normal and the mutant NBD1 domains as they fold, the authors were able to determine critical pairs of amino acid residues that must come together for NBD1 to fold correctly. These interactions are modulators of CFTR folding, and hence, they are potential modulators of CF.

"Computer simulations approximate our understanding of natural phenomena. That our simulations correlated with known experimental studies is remarkable," Dokholyan said. "More importantly, the molecular details of aberrant NBD1 folding provides guidance for the design of small molecule drugs to correct the most prevalent and pathogenic mutation in CFTR."

The first author of the study is Adrian Serohijos, a graduate student in the department of Physics and Astronomy at UNC and in the Molecular and Cellular Biophysics Program. Other co-authors in the study include John Riordan, Ph.D., co-discoverer of the CFTR gene and professor of biochemistry and biophysics, and Tamas Hegedus, Ph.D. of the UNC Cystic Fibrosis Research Center.

This study was supported in part by grants from the Cystic Fibrosis Foundation, the National Institutes of Health, and the American Heart Association.

Journal reference: Serohijos AWR, Hegedus T, Riordan JR, Dokholyan NV (2008) Diminished Self-Chaperoning Activity of the DF508 Mutant of CFTR Results in Protein Misfolding. PLoS Comput Biol 4(2): e1000008. doi:10.1371/journal.pcbi.1000008 http://www.ploscompbiol.org/doi/pcbi.1000008


Story Source:

The above story is based on materials provided by Public Library of Science. Note: Materials may be edited for content and length.


Cite This Page:

Public Library of Science. "Key Molecular Basis Of Cystic Fibrosis Identified Through Computer Simulations." ScienceDaily. ScienceDaily, 3 March 2008. <www.sciencedaily.com/releases/2008/02/080229153126.htm>.
Public Library of Science. (2008, March 3). Key Molecular Basis Of Cystic Fibrosis Identified Through Computer Simulations. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2008/02/080229153126.htm
Public Library of Science. "Key Molecular Basis Of Cystic Fibrosis Identified Through Computer Simulations." ScienceDaily. www.sciencedaily.com/releases/2008/02/080229153126.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins