Molecular Dynamics Simulations to Provide New Insights into the Asymmetrical Ammonium Ion Movement Inside of the [d(G<sub>3</sub>T<sub>4</sub>G<sub>4</sub>)]<sub>2</sub> G-Quadruplex DNA Structure
Bibliographic record
Abstract
We have used both adaptive biasing force (ABF) and regular molecular dynamics (MD) simulations to investigate the asymmetrical NH(4)(+) ion movement inside of a bimolecular G-quadruplex DNA structure [d(G(3)T(4)G(4))](2). The free-energy landscapes obtained from ABF MD simulations suggest that the NH(4)(+) ion exiting the [d(G(3)T(4)G(4))](2) G-quadruplex stem in the direction toward the edge-type loop (denoted as the upper direction) experiences a lower free-energy barrier than that toward the diagonal loop (denoted as the lower direction) by approximately 3-4 kcal mol(-1). This result is in qualitative agreement with the previous discovery made by Šket and Plavec on the same G-quadruplex structure from (15)N NMR experiments (J. Am. Chem. Soc. 2007, 129, 8794). In the Na(+) form of the same G-quadruplex, Na(+) ion movement was found to be symmetrical, with a free-energy barrier of only 5-7 kcal mol(-1) to cross all three G-quartets, that is, [d(G(3)T(4)G(4))](2) still exhibits ion-channel-like behaviors for Na(+) ions. On the basis of the new computational results, we hypothesize that the stiffness of a G-quartet is primarily determined by the base stacking interactions within the G-quadruplex stem. Therefore, the structural origin for the asymmetrical NH(4)(+) ion movement in [d(G(3)T(4)G(4))](2) is the presence of two different modes of base stacking around the NH(4)(+) binding sites, a more stable 5'-syn-anti mode between lower and central G-quartets and a less stable 5'-anti-anti mode between upper and central G-quartets. Simulations also suggest that loop topology at the end of a G-quadruplex stem only controls the direction at which an exiting NH(4)(+) ion reaches bulk solution but does not impose significant free-energy barriers.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".