1. Novel Ligands for a Purine Riboswitch Discovered by RNA-Ligand Docking
- Author
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David A. Robinson, David M.J. Lilley, Robert T. Batey, Peter Daldrop, Ruth Brenk, Colin M. Hammond, and Francis E. Reyes
- Subjects
Riboswitch ,Stereochemistry ,Clinical Biochemistry ,Purine riboswitch ,Biology ,Crystallography, X-Ray ,Ligands ,01 natural sciences ,Biochemistry ,Article ,03 medical and health sciences ,Drug Discovery ,Computer Simulation ,Binding site ,Molecular Biology ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Virtual screening ,Binding Sites ,RNA ,General Medicine ,0104 chemical sciences ,3. Good health ,010404 medicinal & biomolecular chemistry ,Protein–ligand docking ,Docking (molecular) ,Searching the conformational space for docking ,Purines ,Molecular Medicine ,Nucleic Acid Conformation - Abstract
Summary 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., Graphical Abstract Highlights ► Using RNA-ligand docking, four new ligands were discovered for a purine riboswitch ► Two of the ligands were based on scaffolds not known to bind to this riboswitch ► Crystal structures were determined that confirm the binding modes of new ligands ► Molecular docking is a promising method for RNA-structure-based ligand design
- Published
- 2011