Assessing the feasibility and stability of uracil base flipping in RNA–small molecule complexes using molecular dynamics simulations

Lauren D. Hagler, Sarah E. Bonson, Philip A. Kocheril, Steven C. Zimmerman

Research output: Contribution to journalArticlepeer-review

Abstract

Small molecules can be used to target RNAs that mediate disease. A fundamental understanding of binding interactions between RNA and small molecules and the structure of their complexes will further inform the design of new targeting agents. Two small molecule ligands were investigated for their ability to recognize the expanded CUG repeat sequence in RNA, the causative agent of myotonic dystrophy type 1. We report the use of molecular dynamics simulations to explore small molecule–RNA complexes and the finding of a stabilized base flipped conformation at UU mismatches. The results of this computational study support experimental observations and suggest that base flipping is feasible for CUG-repeat RNA.

Original languageEnglish (US)
Pages (from-to)261-269
Number of pages9
JournalCanadian Journal of Chemistry
Volume98
Issue number6
DOIs
StatePublished - 2020

Keywords

  • Base flipping
  • Molecular dynamics (MD) simulation
  • RNA-targeting small molecules

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Organic Chemistry

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