Probing the structure and in silico stability of cargo loaded DNA icosahedra using MD simulations

Platonic solids such as polyhedra based on DNA have been deployed for multifarious applications such as RNAi delivery, biological targeting and bioimaging. All of these applications hinge on the capability of DNA polyhedra for molecular display with high spatial precision. Therefore high resolution structural models of such polyhedra are critical to widen their applications in both materials and biology. Here, we present an atomistic model of a well-characterized DNA icosahedron, with demonstrated versatile functionalities in biological systems. We study the structure and dynamics of this DNA icosahedron using fully atomistic molecular dynamics (MD) simulation in explicit water and ions. The major modes of internal motion have been identified using principal component analysis. We provide a quantitative estimate of the radius of gyration (R_g), solvent accessible surface area (SASA) and volume of the icosahedron which is essential to estimate its maximal cargo carrying capacity. Importantly, our simulation of gold nanoparticles (AuNPs) encapsulated within DNA icosahedra revealed enhanced stability of the AuNP loaded DNA icosahedra compared to empty icosahedra. This is consistent with the experimental results that show high yields of cargo-encapsulated DNA icosahedra that have led to its diverse applications for precision targeting. These studies reveal that the stabilizing interactions between the cargo and the DNA scaffold powerfully position DNA polyhedra as targetable nanocapsules for payload delivery. These insights can be exploited for precise molecular display for diverse biological applications.