The design of ligand functionalized inorganic nanoparticles (NPs) that can induce specific structural transitions in nucleic acids (NA) is important for nanotechnology applications including gene delivery and nanoelectronics. However, comprehensive understanding of ligand design principles lies in the cost associated with synthesizing and characterizing diverse ligand chemistries and ability to carefully assess the structural integrity of biomolecules upon interactions with NPs. It is known that the interaction of nucleic acids and nanoparticles may be tuned through changes in nanoparticle size, charge, polarity, or shape. However, the factors that affect structural transitions are not fully understood. We performed atomistic molecular dynamics simulations of the binding of nucleic acids to monolayer-protected gold nanoparticles to elucidate structural changes that take place for nanoparticles and DNA upon binding. Results from these simulations were analyzed to determine modes of DNA and RNA bending with nanoparticles. Our simulations show that highly charged nanoparticles cause DNA to bend with little damage to the helix structure, similar to DNA in the nucleosome. Nanoparticle shape as well as charge is shown to affect the wrapping of nucleic acids with the nanoparticle. Low salt concentrations and high nanoparticle charge cause greater disruptions to DNA structure. We find that the roll parameter is the most important base-pair parameter for DNA bending. Requirements for bending differed significantly between DNA and dsRNA. The degree of DNA bending is controlled by the charge of the NPs, but ligand flexibility played a more significant role in dsRNA bending. These results allowed us to determine the training data for machine learning algorithms and design a novel ligands capable of controlled wrapping of NA around NP. We have shown that the designer gold NPs are capable of wrapping NAs with fine control of binding strength through NP charge and ligand stiffness. These findings are useful for designing gene delivery systems with enhanced biocompatibility and selectivity.

Design of histone-mimic nanoparticles for DNA and RNA compaction using molecular modeling

2019 Spring National Meeting

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