Deciphering nucleotide modification-induced structure and stability changes.

ABSTRACT: Nucleotide modification in RNA controls a bevy of biological processes, including RNA degradation, gene expression, and gene editing. In turn, misregulation of modified nucleotides is associated with a host of chronic diseases and disorders. However, the molecular mechanisms driving these processes remain poorly understood. To partially address this knowledge gap, we used alchemical and temperature replica exchange molecular dynamics (TREMD) simulations on an RNA duplex and an analogous hairpin to probe the structural effects of modified and/or mutant nucleotides. The simulations successfully predict the modification/mutation-induced relative free energy change for complementary duplex formation, and structural analyses highlight mechanisms driving stability changes. Furthermore, TREMD sim

SUBMITTER: Hurst T 

PROVIDER: S-EPMC8583165 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature