2021 Virtual Undergraduate Research Symposium
2021 Virtual Undergraduate Research Symposium
Sigma-Hole Bonding Unnatural Base Pairs
Sigma-Hole Bonding Unnatural Base Pairs
2ND PLACE ORAL TALK
PROJECT NUMBER: 22 | AUTHORS: Tara Buzinski, Chemical and Biological Engineering and Michael Melville, Chemistry
MENTOR: Mike McGuirk, Chemistry
ABSTRACT
The Global Datasphere is projected to hit 175 zettabytes by 2025 [1]. Physically storing this quantity of data would require an incredible amount of space that conventional storage methods cannot provide. This reality has motivated the exploration of alternative storage methods. DNA has been presented as a viable solution to this problem. Studies have shown that DNA has a volumetric density one thousand times that of current platforms. While retaining the canonical bases of A, T, G, and C we propose the introduction of unnatural base pairs based on sigma-hole bonding to boost the efficiency of DNA as a storage media. Sigma holes are a novel type of noncovalent interaction that is functionally analogous to hydrogen bonding. In this interaction, a region of low electron density on an electropositive donor atom interacts with regions of negative electrostatic potential with high directionality and stability [2]. In this project, we have specifically focused on the subtype of sigma-hole bonding that utilizes halogens as the donor atom. To get an idea of viable synthetic targets, computational studies utilizing density functional theory were performed on native bases substituted with halogens. These studies determined that halogen bonding is a thermodynamically and geometrically viable force for base pairing in the native DNA system if incorporated logically.
[1] Reinsel, D.; Gantz, J.; Rydning, J. The Digitization of the World from Edge to Core. 2018, 28.
[2] Cavallo, G.; Metrangolo, P.; Milani, R.; Pilati, T.; Priimagi, A.; Resnati, G.; Terraneo, G. Chem. Rev. 2016, 116, 2478-2601.
PRESENTATION
AUTHOR BIOGRAPHY
Tara is a third-year student in the chemical and biological engineering department at Mines. She is set to graduate in December 2021 with a major in chemical engineering and a minor in biomedical engineering. Tara joined the McGuirk group in spring 2020 as an undergraduate researcher and has thoroughly enjoyed the work she’s done in exploring fundamental chemistry concepts like sigma-hole bonding and its applications in unnatural DNA base pairs. After graduation, Tara hopes to pursue a graduate degree in the biological sciences.
Michael arrived at Mines in the Fall of 2019 as a transfer student from California and is currently a senior in the chemistry department. Michael is set to graduate in Fall 2021 with a degree in biochemistry. Since his arrival at Mines, Michael’s research has been primarily focused around DNA and the possibility of expanding the genetic alphabet. In the future, Michael hopes to shift his research focus to medicinal chemistry.
Awesome work! I really enjoyed your presentation, especially all of the visuals. Coming from the perspective of someone not in chemical engineering, I am curious if you can elaborate more on what the process of doing point modifications entails, since it seems like most calculations were performed using modeling software. Great work!
Thanks Emily! Basically, each base pair is held together with hydrogen bonds. (A–T has 2 and G–C has 3). We picked one bond to modify at a time, usually changing the hydrogen bond donating group to a halogen. By designing each set of calculations so that only one bond was modified at a time, we could track the trends in energy and geometry, and tie each result back to a specific modification. In the software we used, this is as simple as deleting one or multiple atoms and adding a different one.
This was an interesting talk. I hadn’t considered using DNA to store data but that seems like a really fruitful and creative application of DNA. Do you suspect that any particular halogen will function better on an unnatural base pair? How would you make sure that one of your unnatural base pairs won’t pair up with a natural base pair? I enjoyed your talk. Thank you.
Thanks for your questions Griffin! Yes, we have seen that iodine tends to have stronger interactions due to its greater polarizability, leading to a more positive region of electrostatic potential. An ESP map provided in the slide “Utilizing sigma-holes to expand the genetic alphabet” shows the presence of the sigma-hole on an iodine atom — this sigma hole is much more obvious in iodine than the other halogens.
As for your other question, we are still working on that! We have considered using soft/hard acid/base theory to direct the fidelity of the base pairs, where “soft” (more polarizable) acids and bases are more likely to interact with each other than with “hard” acids and bases. Ensuring fidelity in base pairs is definitely an important aspect of unnatural base pairs, and there are a lot of other possibilities to explore!