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:4/19/2017)... The global military biometrics market ... by the presence of several large global players. The ... major players - 3M Cogent, NEC Corporation, M2SYS Technology, ... 61% of the global military biometric market in 2016. ... military biometrics market boast global presence, which has catapulted ...
(Date:4/11/2017)... BEACH GARDENS, Fla. , April 11, 2017 ... identity management and secure authentication solutions, today announced ... contract by Intelligence Advanced Research Projects Activity (IARPA) ... for IARPA,s Thor program. "Innovation has ... onset and IARPA,s Thor program will allow us ...
(Date:4/5/2017)...  The Allen Institute for Cell Science today announces ... portal and dynamic digital window into the human cell. ... application of deep learning to create predictive models of ... a growing suite of powerful tools. The Allen Cell ... publicly available resources created and shared by the Allen ...
Breaking Biology News(10 mins):
(Date:4/27/2017)... ... April 27, 2017 , ... ... Borlaug CAST Communication Award goes to Jayson Lusk, a consummate communicator who promotes ... media to advocate for science, as he explains how innovation and growth in ...
(Date:4/26/2017)... SAN DIEGO, CALIF. (PRWEB) , ... April 26, ... ... Mother’s Day? Lajollacooks4u, San Diego’s premiere team-building and cooking events company, offers ... cooking classes. , Menus specialize in California cuisine, and guests leave inspired ...
(Date:4/26/2017)... ... April 25, 2017 , ... LABS, Inc. (LABS) announced in December 2016 ... extensive test menu: Nucleic Acid Testing (NAT) for ZIKV; and Enzyme Immunoassays (EIAs) specific ... offer NAT screening for blood donors under an Investigational New Drug (IND) study protocol. ...
(Date:4/26/2017)... Va. (PRWEB) , ... April 26, 2017 , ... ... make headlines and drive high-level conversations among healthcare industry stakeholders, the discussion surrounding ... Environment – taking place May 15-18, 2017 in Los Angeles, Calif. Hosted by ...
Breaking Biology Technology: