Computing Nonequilibrium Conformational Dynamics of Structured Nucleic Acid Assemblies.

Area of Science:

• Biophysics
• Computational Biology
• Nanotechnology

Background:

• Synthetic nucleic acids form precise 3D nanostructures, organizing functional molecules.
• These assemblies exhibit complex dynamics crucial for function, but are hard to simulate.
• All-atom molecular dynamics struggle with the long time and large length scales of high molecular weight assemblies.

Purpose of the Study:

• To present a computational framework for computing the overdamped conformational dynamics of structured nucleic acid assemblies.
• To apply this framework to DNA nanostructures of varying sizes, from tweezers to large origami objects.
• To enable the study of long time-scale and large length-scale motions in synthetic nucleic acid assemblies.

Main Methods:

• Developed a computational framework combining a mechanical finite element model for DNA nanostructures.
• Integrated an implicit solvent model to simulate Brownian dynamics or compute Brownian modes.
• Applied the framework to DNA tweezers, a nine-layer DNA origami ring, and a pointer-shaped DNA origami object.

Main Results:

• Successfully simulated hundreds of microseconds of Brownian dynamics for a large DNA origami ring.
• Predicted the first ten Brownian modes for a pointer-shaped DNA origami object.
• Validated computational results against all-atom molecular dynamics simulations for a DNA tweezer.

Conclusions:

• The developed computational framework efficiently captures the conformational dynamics of large DNA nanostructures.
• This approach overcomes limitations of traditional methods for simulating long time-scale and large length-scale motions.
• Enables deeper understanding of the structure-dynamics-function relationship in synthetic nucleic acid assemblies.