ANNaMo: Coarse-grained modeling for folding and assembly of RNA and DNA systems

Area of Science:

• Biophysics
• Computational Biology
• Bionanotechnology

Background:

• Nucleic acid folding is vital for biological functions and bionanotechnology.
• Current high-resolution models face computational limitations for studying folding dynamics over relevant timescales and system sizes.

Purpose of the Study:

• To introduce a novel coarse-grained model for simulating nucleic acid folding dynamics.
• To enable simulations at scales previously inaccessible to more detailed models.

Main Methods:

• Developed a coarse-grained model representing three nucleotides as a patchy particle.
• Parameterized the model using established nearest-neighbor models.
• Incorporated reduced degrees of freedom and a bond-swapping mechanism for enhanced simulation efficiency.

Main Results:

• Successfully simulated DNA hairpin thermodynamics, MMTV pseudoknot folding, and RNA tile folding.
• Validated the model by accurately reproducing experimental melting temperatures of oligomers.
• Demonstrated the model's ability to capture the dependence of displacement rates on toehold length in toehold-mediated displacement processes.

Conclusions:

• The new coarse-grained model effectively simulates nucleic acid folding dynamics.
• The model's performance is validated by its ability to reproduce experimental data and compare favorably with existing models.
• This advancement opens new possibilities for studying complex nucleic acid structures and processes in bionanotechnology and molecular computing.