Molecular Dynamical Investigation of the 7,8-dihydro-8-oxoguanine Mutation in dsDNA
Bibliographic record
Abstract
Background: The oxidization of a Guanine (G) base pair to 7,8-dihydro-8-oxoguanine (OG) is one of the most common DNA mutations. OG mutations can undergo a regular Watson-Crick base-pairing, or a reverse Hoogsteen (HG) base-pairing, especially in OG:A mismatches. While the causes of these mutations are well-understood, the kinetic and energetic characteristics of this new pseudo-base have never been fully investigated, especially at temperatures around biological function (17-37°C). Methods: We created a simulation to derive the Free Energy Surface (FES) of OG:C and OG:A Hoogsteen to Watson-Crick base-pair (bp) transitions under multiple temperatures, relative to 2 collective geometric variables: the dihedral Chi and the pseudo-dihedral CPD angle. To make the simulation, we used the relatively recent Metadynamics algorithms in conjunction with GROMACS 2020.2. Results: The lowest free energy increased linearly with increasing temperatures (17-37°C). Major Chi and CPD rotations at these minima varied heavily for 27°C and 32°C (the largest was seen in the former), but stayed relatively similar for other temperatures, indicating a highly sensitive relationship to temperature, likely due to DNA flexibility, quantum mechanical (QM) effects, and hydrogen bonding. Free energies had a weak negative linear relationship, and free energy hypersurfaces were given for studied temperatures of 17-37°C. Human body temperature (37°C) results were also included and explained. The simulations showed why OG:A Hoogsteen bps often occur in organisms and are energetically preferable to standard Watson-Crick. OG:C HG base pairings are determined to likely be not as common as OG:A HG. Limitations: Future investigations must focus on discovering rate constants of these base-pairs, as time constraints did not permit them to be done here, as well as more QM-focused simulations.
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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 | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".