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 (GaMD) 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 (SAR) studies and transverse relaxation measurements by NMR spectroscopy. We furt

SUBMITTER: Hegde S 

PROVIDER: S-EPMC11507752 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature