Periodic Reporting for period 1 - NMRSIGN (NMR insights on the soluble Guanylyl Cyclase conformational dynamics to illuminate the SIGNaling pathway)
Periodo di rendicontazione: 2018-08-01 al 2020-07-31
The H-NOX domain of sGC is a hot target for drug discovery because it appears to play a pivotal role in the control of a variety of physiological processes in several signal transduction pathways, with a significant impact on cardiovascular system. NMRSIGN investigates the changes in the structure and dynamics of H-NOX domain upon ligand binding using advanced state-of-the-art NMR techniques, molecular dynamics simulations and free energy calculations. This novel approach of combining NMR and computational MD data to identify receptor conformations that play a major role in biomolecular recognition before commencing the structure-based virtual screening is expected to have a major impact in the field of drug design.
The results obtained have been disseminated to the scientific community through:
1) Open-access publication, “Backbone and side chain NMR assignments of the H-NOX domain from Nostoc sp. in complex with BAY58-2667 (cinaciguat)” published in the Biomolecular NMR Assignments (BNMR).
2) An oral presentation at the University of Edinburgh, School of Chemistry, 22 January 2019, Edinburgh, UK.
3) An oral presentation with the title “Solution NMR spectroscopy and enhanced conformational sampling computational approaches to study the H-NOX domain of soluble guanylate cyclase” at the Edinburgh Parallel Computing Centre, 28 February 2019, Edinburgh, UK.
4) Poster presentation with the title “NMR insights into the structural and functional properties of soluble guanylate cyclase (sGC)”, at the 3rd Symposium “Chemistry at the Interface of Biology and Medicine”, September 23-26, 2019, Department of Pharmacy, University of Patras, Greece.