A coarse-grained lattice model of DNA oligonucleotides is proposed to investigate how fundamental thermodynamic processes are encoded by the nucleobase sequence at the microscopic level, and to elucidate the general mechanisms by which single-stranded oligonucleotides hybridize to their complements either in solution or when tethered to nanoparticles.

Molecular simulations based on a high-coordination cubic lattice are performed using the Monte Carlo method. The dependence of the model's thermal stability on sequence complementarity is shown to be qualitatively consistent with experiment and statistical mechanical models. From the analysis of the statistical distribution of base-paired states and of the associated free-energy landscapes, two general hybridization scenarios are found. For sequences that do not follow a two-state process, hybridization is weakly cooperative and proceeds in multiple sequential steps involving stable intermediates with increasing number of paired bases. In contrast, sequences that conform to two-state thermodynamics exhibit moderately rough landscapes, in which multiple metastable intermediates appear over broad free-energy barriers. These intermediates correspond to duplex species that bridge the configurational and energetic gaps between duplex and denatured states with minimal loss of conformational entropy, and lead to a strongly cooperative hybridization. Remarkably, two-state thermodynamic signatures are generally observed in both scenarios.

The role of cooperativity in the assembly of nanoparticles tethered with model DNA oligonucleotides is similarly addressed with the Monte Carlo method, where nanoparticles are represented as finely discretized hard-core spheres on a cubic lattice. The energetic and structural mechanisms of self-assembling are investigated by simulating the aggregation of small “satellite” particles from the bulk onto a large “core” particle. A remarkable enhancement of the system's thermal stability is attained by increasing the number of strands per satellite particle available to hybridize with those on the core particle. This cooperative process is driven by the formation of multiple bridging duplexes under favorable conditions of reduced translational entropy and the resultant energetic compensation; this behavior rapidly weakens above a certain threshold of linker strands per satellite particle. Cooperativity also enhances the structural organization of the assemblies by systematically narrowing the radial distribution of the satellite particles bound the core.