Structure and conformational dynamics of scaffolded DNA origami nanoparticles

Area of Science:

• Nanotechnology
• Biotechnology
• Computational Biology

Background:

• Synthetic DNA is a programmable nanoscale material for self-assembling 3D structures.
• Double crossover (DX) motifs enable DNA nanoparticle synthesis (5-100 nm) for biotechnology.
• Computational modeling of DNA nanoparticle dynamics is challenging due to long relaxation times.

Purpose of the Study:

• To elucidate the fine-scale and global conformational structure and dynamics of DX-based DNA nanoparticles.
• To develop an efficient computational framework for predicting structural and mechanical properties of DNA origami assemblies.

Main Methods:

• Applied all-atom molecular dynamics and coarse-grained finite element modeling.
• Utilized a coarse-grained model with secondary structural motifs to predict equilibrium structures.
• Compared coarse-grained models with 3D cryo-electron microscopy and all-atom simulations.

Main Results:

• Predicted equilibrium solution structures for 45 DX-based DNA origami nanoparticles (e.g., tetrahedron, octahedron).
• Elucidated non-intuitive atomic-level structural details of DX-based DNA nanoparticles.
• Validated coarse-grained models against experimental and all-atom simulation data.

Conclusions:

• Developed a general framework for efficient computational prediction of DNA nanoparticle properties.
• Demonstrated the utility of coarse-grained modeling for understanding complex DNA assemblies.
• Provided insights into structural and mechanical properties inaccessible to all-atom models alone.