title: Molecular modelling and molecular dynamics of CFTR.
abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a member of the ATP-binding cassette (ABC) transporter superfamily that functions as an ATP-gated channel. Considerable progress has been made over the last years in the understanding of the molecular basis of the CFTR functions, as well as dysfunctions causing the common genetic disease cystic fibrosis (CF). This review provides a global overview of the theoretical studies that have been performed so far, especially molecular modelling and molecular dynamics (MD) simulations. A special emphasis is placed on the CFTR-specific evolution of an ABC transporter framework towards a channel function, as well as on the understanding of the effects of disease-causing mutations and their specific modulation. This in silico work should help structure-based drug discovery and design, with a view to develop CFTR-specific pharmacotherapeutic approaches for the treatment of CF in the context of precision medicine.
authors.affiliation: UMR CNRS 7590, Museum National d'Histoire Naturelle, IRD UMR 206, IUC, Case 115, IMPMC, Sorbonne Universités, UPMC Univ Paris 06, 4 Place Jussieu, 75005, Paris Cedex 05, France. isabelle.callebaut@impmc.upmc.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.affiliation: UMR CNRS 7590, Museum National d'Histoire Naturelle, IRD UMR 206, IUC, Case 115, IMPMC, Sorbonne Universités, UPMC Univ Paris 06, 4 Place Jussieu, 75005, Paris Cedex 05, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Hoffmann
authors.affiliation: INSERM U1078, SFR ScInBioS, Université de Bretagne Occidentale, Brest, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lehn
authors.affiliation: UMR CNRS 7590, Museum National d'Histoire Naturelle, IRD UMR 206, IUC, Case 115, IMPMC, Sorbonne Universités, UPMC Univ Paris 06, 4 Place Jussieu, 75005, Paris Cedex 05, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mornon
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011487:Protein Conformation
chemical_list: D008024:Ligands; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: ABC transporte; ABCC7; Cystic fibrosis; Ion channel; Modulators; Mutations