Navigation Links
Computer simulations point to key molecular basis of cystic fibrosis
Date:2/29/2008

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, published February 29 in the open-access journal PLoS Computational Biology, 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.


'/>"/>

Contact: Mary Kohut
Press@plos.org
415-568-3457
Public Library of Science
Source:Eurekalert

Related biology news :

1. Primate behavior explained by computer agents
2. Computer program traces ancestry using anonymous DNA samples
3. A computer for your mouse!
4. New approach builds better proteins inside a computer
5. Computer solution to delivery problem
6. MSU researcher helps develop computer game for Ugandan children recovering from cerebral malaria
7. Improving detection of nuclear smuggling goal of computer model of mechanical engineer
8. Computer savvy canines
9. Brain-computer link systems on the brink of breakthrough, study finds
10. Computer learns dogspeak
11. Computer-based tool aids research, helps thwart questionable publication practices
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/22/2016)... , June 22, 2016  The American College of ... Trade Show Executive Magazine as one of the fastest-growing ... May 25-27 at the Bellagio in Las Vegas ... the highest percentage of growth in each of the following ... exhibiting companies and number of attendees. The 2015 ACMG Annual ...
(Date:6/20/2016)... -- Securus Technologies, a leading provider of civil ... investigation, corrections and monitoring announced that after exhaustive ... the final acceptance by all three (3) Department ... (MAS) installed. Furthermore, Securus will have contracts for ... October, 2016. MAS distinguishes between legitimate wireless device ...
(Date:6/9/2016)... -- Paris Police Prefecture ... to ensure the safety of people and operations in several ... tournament Teleste, an international technology group specialised in ... that its video security solution will be utilised by ... safety across the country. The system roll-out is scheduled for ...
Breaking Biology News(10 mins):
(Date:6/23/2016)...  The Biodesign Challenge (BDC), a university competition that ... living systems and biotechnology, announced its winning teams at ... New York City . The teams, ... at MoMA,s Celeste Bartos Theater during the daylong summit. ... curator of architecture and design, and Suzanne Lee ...
(Date:6/23/2016)... ... 23, 2016 , ... In a new case report published today in STEM ... who developed lymphedema after being treated for breast cancer benefitted from an injection of ... dealing with this debilitating, frequent side effect of cancer treatment. , Lymphedema ...
(Date:6/23/2016)... On Wednesday, June 22, 2016, the ... the Dow Jones Industrial Average edged 0.27% lower to finish ... 0.17%. Stock-Callers.com has initiated coverage on the following equities: Infinity ... NKTR ), Aralez Pharmaceuticals Inc. (NASDAQ: ... ). Learn more about these stocks by accessing their free ...
(Date:6/23/2016)... -- Amgen (NASDAQ: AMGN ) today announced a ... sciences incubator to accelerate the development of new therapies ... QB3@953 was created to help high-potential life science and ... stage organizations - access to laboratory infrastructure. ... "Amgen Golden Ticket" awards, providing each winner with one ...
Breaking Biology Technology: