Probing the Structure and in Silico Stability of Cargo Loaded DNA Icosahedron using MD Simulations

摘要

Platonic solids such as polyhedra based on DNA have been deployed formultifarious applications such as RNAi delivery, biological targeting andbioimaging. All of these applications hinge on the capability of DNA polyhedrafor molecular display with high spatial precision. Therefore high resolutionstructural models of such polyhedra are critical to widen their applications inboth materials and biology. Here, we present an atomistic model of awell-characterized DNA icosahedron, with demonstrated versatile functionalitiesin biological systems. We study the structure and dynamics of this DNAicosahedron using fully atomistic molecular dynamics simulation in explicitwater and ions. The major modes of internal motion have been identified usingprincipal component analysis. We provide a quantitative estimate of the radiusof gyration (Rg), solvent accessible surface area (SASA) and volume of theicosahedron which is essential to estimate its maximal cargo carrying capacity.Importantly, our simulation of gold nanoparticles (AuNP) encapsulated withinDNA icosahedra revealed enhanced stability of the AuNP loaded DNA icosahedracompared to empty icosahedra. This is consistent with experimental results thatshow high yields of cargo-encapsulated DNA icosahedra that have led to itsdiverse applications for precision targeting. These studies reveal that thestabilizing interactions between the cargo and the DNA scaffold powerfullypositions DNA polyhedra as targetable nanocapsules for payload delivery. Theseinsights can be exploited for precise molecular display for diverse biologicalapplications.