Multi-scale coarse-graining for the study of assembly pathways in DNA-brick self-assembly

Area of Science:

• Biophysics
• Materials Science
• Computational Chemistry

Background:

• Single-stranded DNA tiles enable the creation of intricate nanoscale structures.
• Studying the assembly mechanisms of these structures requires models that operate at relevant time and length scales.

Purpose of the Study:

• To develop a coarse-grained kinetic model for simulating DNA tile assembly.
• To accurately predict critical assembly parameters like temperature and nucleation barriers.
• To investigate the assembly pathways and intermediate structures of DNA assemblies.

Main Methods:

• A two-step coarse-graining approach was employed, utilizing detailed thermodynamic calculations from the oxDNA (nucleotide-based DNA model) to parameterize a coarser kinetic model.
• The model was tested by simulating the assembly of a 2D target structure composed of 334 unique 42-nucleotide DNA strands.
• The simulation was performed without adjustable parameters.

Main Results:

• The model accurately reproduced the critical assembly temperature observed in experiments.
• Detailed analysis of nucleation barriers and critical nucleus shapes was performed.
• Assembly intermediates were found to be compact and highly connected.

Conclusions:

• The developed coarse-grained model effectively simulates DNA tile assembly at relevant scales.
• Classical nucleation theory accurately describes the nucleation barrier near the critical assembly temperature.
• The model provides insights into the fundamental mechanisms governing DNA self-assembly.