Interrogating RNA-Small Molecule Interactions with Structure Probing and Artificial Intelligence-Augmented Molecular Simulations.

ABSTRACT: While there is increasing interest in the study of RNA as a therapeutic target, efforts to understand RNA-ligand recognition at the molecular level lag far behind our understanding of protein-ligand recognition. This problem is complicated due to the more than 10 orders of magnitude in time scales involved in RNA dynamics and ligand binding events, making it not straightforward to design experiments or simulations. Here, we make use of artificial intelligence (AI)-augmented molecular dynamics simulations to directly observe ligand dissociation for cognate and synthetic ligands from a riboswitch system. The site-specific flexibility profiles from our simulations are compared with in vitro measurements of flexibility using selective 2' hydroxyl acylation analyzed by primer extension a

SUBMITTER: Wang Y 

PROVIDER: S-EPMC9228567 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature