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 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".