Comparative computational analysis of cystic fibrosis transmembrane conductance regulator protein to treat lung infections

Abstract

The screening of cystic fibrosis transmembrane conductance regulator (CFTR) mutations and analysing such mutations acts as a marker in the diagnosis of cystic fibrosis (CF). The third most common mutation Glycine-to-aspartic acid missense mutation at codon 551 (G551D-CFTR) in the highly conserved signature sequence of each CFTR’s NBD (nucleotide binding domain) completely inhibits the ability of ATP to perform the channel activity presents a severe clinical phenotype. While this is one route, another route that affects and causes CF was identified as the chronic infection by Pseudomonas aeruginosa. Hence, comparative pathway analysis between the host and the pathogen that would facilitate the identification of unique targets for the pathogen was attempted, which yielded with, D-alanine metabolism in Pseudomonas aeruginosa to inhibit the bacterial cell wall synthesis resulting in death. Therefore, insilico molecular docking analysis was carried out with two interests: 1 to target both wild-type and mutant-type CFTR with the quinolizinium derivatives to determine the most potent compound 2 to target alanine racemase with different antimicrobial drugs interaction with the target using the Schrodinger product GLIDE. However, both the predicted results have given certain interesting observation, which requires further research to account for clinical extension to design drugs for cystic fibrosis and of course for lung infections that occur under cystic fibrosis condition.