Coarse-grained simulation study of sequence effects on DNA hybridization in a concentrated environment

Area of Science:

• Biophysics
• Computational Biology
• Materials Science

Background:

• DNA self-assembly is crucial for nanotechnology.
• Understanding its thermodynamics and kinetics is key for programmability.
• Existing models may not fully capture sequence and solvent effects.

Purpose of the Study:

• To develop a novel coarse-grained model for DNA self-assembly.
• To elucidate the thermodynamics and kinetic mechanisms governing DNA hybridization and assembly.
• To investigate the influence of sequence and solvent conditions on DNA self-assembly.

Main Methods:

• Developed a novel coarse-grained model for DNA.
• Performed constant-temperature simulations of DNA hybridization.
• Conducted large-scale simulations at high DNA strand concentrations.

Main Results:

• The model accurately predicts sequence-dependent thermal properties and salt-dependent persistence length of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA).
• Two hybridization mechanisms were identified: slow slithering and faster zippering.
• DNA self-assembly is enthalpically driven, occurring via multiple pathways including strand displacement.
• Sequence influences pathway dominance and aggregate size distribution.

Conclusions:

• The developed coarse-grained model provides insights into DNA self-assembly thermodynamics and kinetics.
• Sequence is a critical factor in controlling DNA self-assembly pathways and outcomes.
• The simulation tool is promising for DNA nanotechnology research.