Refining the RNA Force Field with Small-Angle X-ray Scattering of Helix-Junction-Helix RNA

Weiwei He, Nawavi Naleem, Diego Kleiman, Serdal Kirmizialtin

Research output: Contribution to journalArticlepeer-review


The growing recognition of the functional and therapeutic roles played by RNA and the difficulties in gaining atomic-level insights by experiments are paving the way for all-atom simulations of RNA. One of the main impediments to the use of all-atom simulations is the imbalance between the energy terms of the RNA force fields. Through exhaustive sampling of an RNA helix-junction-helix (HJH) model using enhanced sampling, we critically assessed the select Amber force fields against small-angle X-ray scattering (SAXS) experiments. The tested AMBER99SB, DES-AMBER, and CUFIX force fields show deviations from measured profiles. First, we identified parameters leading to inconsistencies. Then, as a way to balance the forces governing RNA folding, we adopted strategies to refine hydrogen bonding, backbone, and base-stacking parameters. We validated the modified force field (HB-CUFIX) against SAXS data of the HJH model in different ionic strengths. Moreover, we tested a set of independent RNA systems to cross-validate the force field. Overall, HB-CUFIX demonstrates improved performance in studying thermodynamics and structural properties of realistic RNA motifs.

Original languageEnglish (US)
Pages (from-to)3400-3408
Number of pages9
JournalJournal of Physical Chemistry Letters
Issue number15
StatePublished - Apr 21 2022

ASJC Scopus subject areas

  • General Materials Science
  • Physical and Theoretical Chemistry


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