title: Novel ligands for a purine riboswitch discovered by RNA-ligand docking.
abstract: The increasing number of RNA crystal structures enables a structure-based approach to the discovery of new RNA-binding ligands. To develop the poorly explored area of RNA-ligand docking, we have conducted a virtual screening exercise for a purine riboswitch to probe the strengths and weaknesses of RNA-ligand docking. Using a standard protein-ligand docking program with only minor modifications, four new ligands with binding affinities in the micromolar range were identified, including two compounds based on molecular scaffolds not resembling known ligands. RNA-ligand docking performed comparably to protein-ligand docking indicating that this approach is a promising option to explore the wealth of RNA structures for structure-based ligand design.
authors: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors: Peter
authors: P
authors: Daldrop
authors: Francis E
authors: FE
authors: Reyes
authors: David A
authors: DA
authors: Robinson
authors: Colin M
authors: CM
authors: Hammond
authors: David M
authors: DM
authors: Lilley
authors: Robert T
authors: RT
authors: Batey
authors: Ruth
authors: R
authors: Brenk
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008024:Ligands; D009690:Nucleic Acid Conformation; D011687:Purines / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D058928:Riboswitch
chemical_list: D008024:Ligands; D011687:Purines; D058928:Riboswitch; D012313:RNA; C030985:purine