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

TL;DR

This paper introduces a multi-scale coarse-graining method combining thermodynamic and kinetic models to study DNA-brick assembly pathways, accurately predicting critical temperatures and nucleation barriers.

Contribution

The authors develop a novel two-step coarse-graining approach that bridges detailed thermodynamic calculations with scalable kinetic modeling for DNA self-assembly.

Findings

Model accurately predicts critical assembly temperature close to experiments.

Reveals detailed nucleation barriers and shapes of critical nuclei.

Assembly intermediates are compact and highly connected.

Abstract

Inspired by recent successes using single-stranded DNA tiles to produce complex structures, we develop a two-step coarse-graining approach that uses detailed thermodynamic calculations with oxDNA, a nucleotide-based model of DNA, to parametrize a coarser kinetic model that can reach the time and length scales needed to study the assembly mechanisms of these structures. We test the model by performing a detailed study of the assembly pathways for a two-dimensional target structure made up of 334 unique strands each of which are 42 nucleotides long. Without adjustable parameters, the model reproduces a critical temperature for the formation of the assembly that is close to the temperature at which assembly first occurs in experiments. Furthermore, the model allows us to investigate in detail the nucleation barriers and the distribution of critical nucleus shapes for the assembly of a single target structure. The assembly intermediates are compact and highly connected (although not maximally so) and classical nucleation theory provides a good fit to the height and shape of the nucleation barrier at temperatures close to where assembly first occurs.