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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.

SUBMITTER: Daldrop P

PROVIDER: S-EPMC3119931 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Novel ligands for a purine riboswitch discovered by RNA-ligand docking.

Daldrop Peter P Reyes Francis E FE Robinson David A DA Hammond Colin M CM Lilley David M DM Batey Robert T RT Brenk Ruth R

Chemistry & biology 20110301 3

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 compou ...[more]

PMID: 21439477

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