Visualizing RNA Structures by SAXS-Driven MD Simulations.

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• The function of biomolecules, particularly RNA, is intrinsically tied to their dynamic structures.
• Determining atomic-level structural ensembles often requires integrating experimental and computational methods.

Purpose of the Study:

• To develop and apply a combined molecular dynamics (MD) simulation and small-angle X-ray scattering (SAXS) approach for resolving RNA structural dynamics.
• To accurately construct conformational ensembles of RNA molecules by integrating experimental data with simulations.

Main Methods:

• Utilized all-atom MD simulations coupled with SAXS experiments.
• Employed RNA-tailored re-weighting and biasing techniques.
• Studied a SAM-I riboswitch and a two-way junction RNA to demonstrate the approach.

Main Results:

• Observed dynamic conformational changes in the SAM-I riboswitch upon ligand (SAM) and cation (Mg2+) binding, with stabilization of compact states.
• Demonstrated that the absence of SAM or Mg2+ leads to riboswitch expansion due to loss of tertiary contacts.
• Showcased the sensitivity of RNA structure to ionic strength using a helix junction helix (HJH) model, exhibiting non-monotonic compaction.

Conclusions:

• The integration of SAXS experiments and MD simulations enables accurate characterization of RNA conformational ensembles.
• This physics-based, experimentally guided approach provides valuable biophysical insights into RNA structural dynamics.
• SAXS-guided MD simulations present a powerful strategy for investigating the complex structural dynamics of RNA molecules.