Mechanistic studies of small molecule ligands selective to RNA single G bulges.

ABSTRACT: Small-molecule RNA binders have emerged as an important pharmacological modality. A profound understanding of the ligand selectivity, binding mode, and influential factors governing ligand engagement with RNA targets is the foundation for rational ligand design. Here, we report a novel class of coumarin derivatives exhibiting selective binding affinity towards single G RNA bulges. Harnessing the computational power of all-atom Gaussian accelerated molecular dynamics simulations, we unveiled a rare minor groove binding mode of the ligand with a key interaction between the coumarin moiety and the G bulge. This predicted binding mode is consistent with results obtained from structure-activity relationship studies and transverse relaxation measurements by nuclear magnetic resonance spectroscop

SUBMITTER: Hegde S 

PROVIDER: S-EPMC12188297 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature