To date, the development of new compounds able to correct D508-CFTR protein is based on structural studies and virtual screening of static molecular models despite, in vivo, CFTR is subject to complex conformational transitions leading to the opening of the chloride channel. Our proposal is to develop and validate 3D dynamic conformational models flanked to SPR analysis for the identification and design of new DF508 correctors. A massive library of small chemical compounds (ligands, prodrugs) will be built from the Zinc online database (http://zinc.docking.org) containing up to 21 million commercial compounds. New techniques will be applied to screen and identify lead compounds (Targeted Molecular Dynamics and GPU Accelerated Molecular Dynamics, Real time molecular interaction analysis by Surface Plasmon Resonance, SPR). The technologies optimized by our consortium will be made available for collaboration among the other research groups belonging to the Foundation.