Nothing beats nature’s histones for tightly spooling DNA, but that hasn’t stopped scientists from trying to engineer something better—at least for selected purposes. If scientists were to create custom spindles around which DNA could wrap more tightly, they would likely improve technologies for storing and transporting genetic information, delivering drugs, and building scaffolds for bioelectronics.

At North Carolina State University, researchers are working to pack nucleic acids (NAs) such as DNA and RNA more efficiently. These researchers expect that by characterizing how NAs interact with custom spindles—functionalized nanoparticles—they will learn how to control the shape and structure of DNA and RNA as needed.

Progress reported by the researchers includes the development of a large-scale computer model that accounts for every atom in compaction processes that occur between NAs and functionalized gold nanoparticles. This model was described November 2 in the journal ACS Nano, in an article entitled, “Characterization of Nucleic Acid Compaction with Histone-Mimic Nanoparticles through All-Atom Molecular Dynamics.”

In their model, the researchers manipulated the charge of the gold nanoparticles by adding or removing positively charged ligands—organic molecules attached to the surface of the nanoparticle. This approach allowed the researchers to determine how a nucleic acid would respond to different levels of charge. The researchers also considered how altering solution salt concentration might influence the responses of RNA and DNA to the positively charged nanoparticles (NPs).

“[The] ability of a nanoparticle to bend DNA is directly correlated with the NPs charge and ligand corona shape, where more than 50% charge neutralization and spherical shape of the NP ligand corona ensured the DNA compaction,” wrote the authors. “However, NP with 100% charge neutralization is needed to bend DNA almost as efficiently as the histone octamer.”

“RNA compaction can only be achieved through a combination of highly charged nanoparticles with low salt concentration,” they continued. “Upon interactions with highly charged NPs, DNA bends through periodic variation in groove widths and depths, whereas RNA bends through expansion of the major groove.”

The research team is now building on these findings to design new nanoparticles with different shapes and surface chemistries to get even more control over the shape and structure of nucleic acids.

“Our large-scale models account for every atom involved in the process,” says Nan Li, a Ph.D. student at NC State and co-author of the paper. “This is an example of how we can use advanced computational hardware, such as the GPUs—or graphics processing units—developed for use in videogames, to conduct state-of-the-art scientific simulations.”

“No one has come close to matching nature's efficiency when it comes to wrapping and unwrapping nucleic acids,” added Yaroslava Yingling, Ph.D., an associate professor of materials science and engineering at NC State and corresponding author of the paper. “We're trying to advance our understanding of precisely how that works.”

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