Evidence that Electrostatic Interactions Dictate the Ligand-Induced Arrest of RNA Global Flexibility

摘要

Arresting flexibility to prevent RNA from undergoing functionally important conformational transitions is an established strategy for developing RNA-targeting therapeutics.'1' To understand the role of RNA flexibility in adaptive recognition'2' is also important for the rational design of small molecules that bind their RNA target with high affinity and specificity.'31 Yet few studies have quantitatively examined how RNA-binding therapeutics affect the flexibility of their RNA targets.As a result,little is known about the RNA-ligand interactions that are important for arresting different types of RNA functional flexibility.Here,we provide direct evidence by using NMR residual dipolar couplings (RDCs)'4' that electrostatic interactions play a primary role in dictating the degree to which small molecules arrest global motions in RNA.