[POSTECH research team explored various DNA donor-receptor interactions essential for designing and predicting the next-generation DNA complex structures.]

DNA carries the genetic code of all living organisms and even viruses by forming various complex structures, and deciphering the structural code would be the cornerstone of next-generation diagnostics and therapeutics. Recently, a research team at POSTECH has succeeded in developing a great way to fully understand the DNA complex structures by ab initio calculations.

A POSTECH research team – led by professor Seung Soo Oh and Donghwa Lee with Ph.D. candidates Gyuri Park, Byunghwa Kang, and Soyeon Park in the Department of Materials Science and Engineering – has systematically componentized the donor-acceptor interactions that involve in formation of double, triple, and quadruple helices of DNA using the ab initio calculations, and precisely evaluated a stability trend among Watson-Crick and Hoogsteen base pairing, stacking, and even ion binding. The team also accurately identified the exceptional potassium-ion (K+) preference of G-quadruplex structure, which is well-known to constitute telomeres – aging-related structures within chromosomes – for the first time at an ab initio level.

DNA can assume various structures as a result of interactions at atomic and molecular levels. Understanding the consequences of the interactions could guide development of ways to design complicated DNA constructs for a wide range of applications in the future, so simulation-based researches have been inevitably required. However, until now, previous simulation studies have often failed to properly predict the actual behavior of DNA containing biological genetic information. This is because the specific environment of DNA in aqueous solutions was not fully considered, and the complex interactions with metal ions and water molecules at a molecular level were not systematically investigated, either.

The research team applied the water continuum model to all ab initio calculations to mimic the aqueous environment in nature, examining the interactions not only between DNA bases, but also between water molecules and metal ions. In addition, to precisely analyze the calculated DNA structures, structural factors such as hydrogen bond length, glycosidic vector angle, and twist angle were newly devised and applied.

The research team thoroughly compared the computationally-predicted DNA structures with the experimentally-determined ones, thereby clarifying the function of phosphate backbone during nucleobase ordering. Moreover, the simulation results were highly consistent with the experimental ones by adding up the componentized interaction energies not only in the double helix with relatively simple donor-acceptor interactions but also in the triple or quadruple helices that include more complex interaction components.

According to these results, it has been newly revealed that the interaction energies and structural analyses of DNA double, triple, and quadruple helix structures using the ab initio calculations can be the basis for more elaborate and complex DNA structure designs.

“Through the ab initio calculations, we have successfully simulated various types of donor-receptor interactions acting on the basic form of the double helix and the complex ones of the triple and the quadruple helix,” remarked Professor Donghwa Lee. “It means that even spatiotemporal changes of DNA can be adequately predicted.”

Professor Seung Soo Oh explained, “This research provides key information of design, prediction, and application for the next-generation complex DNA nanoconstructs.” He added, “The simulated tendency of net interaction energies would be highly applicable in various experimental studies such as disease diagnosis and prediction, new drug development, and even anti-aging.”

As published in the latest issue of Nucleic Acids Research, a world-renowned journal on genome research, this study was conducted with the support from the Young Researcher Program of the National Research Foundation of Korea.