(687f) Designing Nanoparticles for Efficient Wrapping of Nucleic Acids

Nanoparticles that can evoke a specific response on nucleic acid structure are important for many applications including bioelectronics and gene delivery. However, design of such effective nanoparticles is not yet fully realized. We perform atomistic molecular dynamics simulations of the binding of monolayer protected gold nanoparticles of varying charge and polarity to nucleic acid molecules. Our objective is to elucidate details such as effect of binding on DNA/RNA helical structure and bending transitions.  Helical analysis of bound DNA strands indicate that DNA binds to weakly charged and polar particles with minimal effect on helical structure. Highly charged particles, however, cause the DNA to bend. Bending causes little disturbance in helical rise or hydrogen bonding between base pairs. Instead, bending of DNA occurs through expansion or compression along the major and minor grooves. RNA interactions with nanoparticles can show different bending behavior due to increased stiffness of the RNA duplex. Salt concentration adds another control over the process. In nature, genomic DNA in eukaryotic cells wraps around positively charged cylindrical histone proteins to form nucleosomes. One way we judge the success of our nanoparticle design by comparing nucleic acid conformations resulting from nanoparticles binding with those of DNA wrapped around histone proteins.