AVS 65th International Symposium & Exhibition
    Biomaterial Interfaces Division Thursday Sessions
       Session BI-ThA

Paper BI-ThA10
Tailoring Interactions at the Nanoparticle-nucleic Acid Interface using Molecular Modelling

Thursday, October 25, 2018, 5:20 pm, Room 101B

Session: Biolubrication and Wear / Women in Bio-surface Science
Presenter: Yaroslava Yingling, North Carolina State University
Authors: M. Manning, North Carolina State University
J.A. Nash, North Carolina State University
Y.G. Yingling, North Carolina State University
Correspondent: Click to Email
The design of nanoparticles (NPs) that can induce specific structural transitions in nucleic acids (NA) is important for nanotechnology applications including gene delivery and nanoelectronics. NP biocompatibility and efficacy is determined by geometry, charge, and surface chemistry. Advancing NPs to the clinic requires optimization, which is prohibitively expensive, and a mechanistic understanding of NP-NA interactions, which remains unknown. This project will advance tailored NP gene delivery by a multiscale optimization employing all-atom molecular dynamics (MD) simulations and leveraging machine learning algorithms. It is known that in biological systems, the binding of cationic proteins induces structural changes in DNA or RNA, which can affect gene expression or cause the compaction of DNA into chromatin. The anionic backbone of the nucleic acids DNA and RNA allow for non-specific electrostatic interactions with cationic proteins, nanoparticles, or dendrimers. 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.