Coarse-Grained Simulations for the Characterization and Optimization of Hybrid Protein-DNA Nanostructures

We present here the combination of experimental and computational modeling tools for the design and characterization of protein-DNA hybrid nanostructures. Our work incorporates several features in the design of these nanostructures: (1) modeling of the protein-DNA linker identity and length; (2) optimizing the design of protein-DNA cages to account for mechanical stresses; (3) probing the incorporation efficiency of protein-DNA conjugates into DNA nanostructures. The modeling tools were experimentally validated using structural characterization methods like cryo-TEM and AFM. Our method can be used for fitting low-resolution electron density maps when structural insights cannot be deciphered from experiments, as well as enable in-silico validation of nanostructured systems before their experimental realization. These tools will facilitate the design of complex hybrid protein-DNA nanostructures that seamlessly integrate the two different biomolecules.