Cystic Fibrosis

Cystic Fibrosis (CF) is a common lethal, genetic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), an epithelial anion channel in several vital organs. Absence of functional CFTR results in imbalanced osmotic equilibrium and subsequent mucus build up - which is prone to infection and eventually lethal. CFTR is an ATP binding cassette (ABC) transporter composed of two transmembrane domains (TMDs), two nucleotide binding domains (NBDs), and an unstructured regulatory domain. The most common patient mutation, deletion of F508 (ΔF508) CFTR, is the primary target for current FDA approved CF therapies. CF therapies work by binding and stabilizing CFTR structure. The recent elucidation of CFTR structures and drug binding sites afford the opportunity for computational modeling of ΔF508 CFTR and structure based CF drug design.