Investigations on the Effects of Co-solvents and Hydrostatic Pressure on the Thermal Stability of Guanine-quadruplex DNA
Bibliographic record
Abstract
Guanine-quadruplexes (GQs) are a non-canonical tetra-helical DNA structure formed in solutions containing certain monovalent cations. These structures form spontaneously in solution by the planar association of four guanines around a central cation, such as potassium or sodium, and the subsequent stacking of these tetrads. GQ DNA may be promising targets for drug design and bio-nanotechnology applications owing to their structural diversity and physical properties, and therefore an understanding of the physical and chemical factors that modulate the stability of these GQs is essential. In this thesis, I investigated using circular dichroism and ultraviolet spectroscopy, through a basic research approach, the effects of co-solvents and hydrostatic pressure on the thermodynamic stability of GQs. The co-solvents dimethyl sulfoxide (DMSO) and urea were shown to have opposing effects on the melting temperature, Tm (an indicator of thermodynamic stability); generally, DMSO stabilized and urea destabilized GQs. In a surprising finding, the addition of molar concentrations of the denaturant urea was found to enhance the stability of the G3T GQ, a GQ considered to be one of the most stable nucleic acid structures in existence. Additional work is required to understand the mechanistic effect of DMSO and urea on GQ stability, and how these co-solvents affect the hydration of GQs. I also characterized the volume of the loop component of GQ DNA, and showed through high pressure volume work that the loops are the primary contributor to the change in volume (ΔV) arising from the folding of oligodeoxyribonucleotides to GQs. The next step to support our hypothesis is to determine the volume of the guanine tetrad region. Both the co-solvent and volume data probe the interactions of water molecules around the GQ, which is crucial in understanding the energetics of any biomolecule in solution. These findings are therefore not only important for the characterization of GQ DNA in various cellular and laboratory environments, but also for furthering our understanding of the fundamental forces that enable life to exist.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".