New Core21 projects 9205-9206

[jadeshi]

Hey all, two new Core21 projects 9205/9206:

Project description:
Cystic fibrosis (CF) is a common inherited genetic disease that currently affects 30,000 individuals in the US and results in significantly impaired lung function in patients. The most common cause of the disease is the deletion of residue F508 in the cystic fibrosis transmembrane conductance regulator protein (CFTR). This residue is located in the first nucleotide binding domain (NBD1) and has been shown to be critical for both local domain folding and domain-domain assembly. As a result, this single-deletion mutant (delF508 CFTR) has significantly impaired folding ability, leading to a critical shortage of functional protein at the cell membrane and onset of CF. Currently, the most potent treatments for the disease have limited efficacy, improving the folding efficiency of delF508 CFTR to only 10-20% of the wild-type and only slightly increasing lung function. In order to improve upon current treatments, the mechanism of action of current drugs must be well-understood.

Recent studies suggest that the CF drug VX-809 (Lumacaftor) acts allosterically to stabilize NBD1 by binding to the first membrane spanning domain (MSD1). This set of projects will simulate the effects of VX-809 and a set of related experimental drugs on MSD1 by examining the conformational changes induced in MSD1 after binding these drugs at select sites. The long term goal of this project is to elucidate the mechanism of action of VX-809 and related drugs, and use this knowledge to develop more efficacious treatments for CF.

Project details:
Stats credit: 24400
Timeout: 7
Deadline: 10
k-factor: 0.75
OS: Win/Linux

Thanks!
Jade