Coarse-grained modelling of supercoiled RNA.

Area of Science:

• Biophysics
• Computational Biology
• Molecular Modeling

Background:

• Double-stranded RNA (dsRNA) exhibits complex mechanical properties influenced by topological constraints like twist and tension.
• Understanding these properties is crucial for various biological processes, including gene regulation and viral replication.
• Recent advances in single-molecule experiments provide new data for validating theoretical models.

Purpose of the Study:

• To investigate the mechanical behavior of double-stranded RNA under varying degrees of twist and tension.
• To validate the coarse-grained oxRNA model against experimental data for dsRNA.
• To predict novel structural transitions and behaviors of dsRNA under supercoiling.

Main Methods:

• Utilized the oxRNA coarse-grained model, incorporating explicit salt-dependence for direct comparison with experiments.
• Simulated dsRNA behavior under controlled twist and stretching forces.
• Analyzed extension curves, buckling transitions, and plectoneme formation.

Main Results:

• The oxRNA model accurately reproduced experimental extension curves as a function of twist and force.
• The model successfully captured the buckling transition and plectoneme structural dynamics.
• Predicted denaturation bubble formation in plectoneme end-loops under negative supercoiling, suggesting sequence-dependent localization.
• Observed a positive twist-stretch coupling constant, aligning with experimental findings.

Conclusions:

• The oxRNA model provides a reliable framework for studying dsRNA mechanics under topological stress.
• The findings offer insights into sequence-specific structural preferences in supercoiled RNA.
• This work bridges computational modeling and experimental observations in RNA biophysics.