Novel Ligands for a Purine Riboswitch Discovered by RNA-Ligand Docking

Peter Daldrop, Francis E. Reyes, David A. Robinson, Colin M. Hammond, David M. Lilley, Robert T. Batey, Ruth Brenk

    Research output: Contribution to journalArticlepeer-review

    65 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)324-335
    Number of pages12
    JournalChemistry & Biology
    Volume18
    Issue number3
    DOIs
    Publication statusPublished - 25 Mar 2011

    Keywords

    • MODEL BINDING-SITE
    • MOLECULAR DOCKING
    • SCORING FUNCTIONS
    • AUTOMATED DOCKING
    • GENE-EXPRESSION
    • DRUG TARGETS
    • RECOGNITION
    • COMPLEXES
    • PROGRAMS
    • GUANINE

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