Exploring the limits of nucleobase expansion: computational design of naphthohomologated (xx-) purines and comparison to the natural and xDNA purines
Bibliographic record
Abstract
The properties of doubly-expanded (xx-) purine analogues are compared to the natural and singly-expanded (x-) purines using quantum chemical (B3LYP, MP2) methods. Purine expansion upon incorporation of a benzene or naphthalene spacer affects the preferred orientation of the base about the glycosidic bond in the corresponding nucleoside to a similar extent. Although the natural purines preferentially adopt the anti orientation with respect to the 2'-deoxyribose moiety, the syn and anti conformations are almost isoenergetic in the case of the expanded analogues. However, the anti/syn rotational barrier either remains similar to or is slightly elevated upon purine expansion, and therefore the expanded analogues will likely display similar rigidity with respect to rotation about the glycosidic bond as the natural purines. The A:T Watson-Crick hydrogen-bond strength is slightly enhanced, while the G:C interaction energy decreases slightly, upon incorporation of either expanded purine. As expected, the largest effect of base expansion occurs on the stacking energies. Specifically, the maximum (most negative) stacking energies in isolated purine dimers formed by aligning the nucleobase centers of mass can be increased by up to 34% by including a single x-purine and by up to 51% by including an xx-purine. Although increases in the purinepurine intrastrand stacking interactions are found even when a simplified duplex model composed of two stacked (hydrogen-bonded) base pairs is considered, the purinepyrimidine stacking energies decrease upon purine expansion. However, the total stability (sum of all hydrogen-bonding and stacking interactions) of natural duplex models is up to 10% and 22% greater for duplexes containing expanded x- and xx-purines respectively, which is mainly due to enhanced inter and intrastrand stacking interactions. Thus, unidirectional expansion in the size of the nucleobase spacer can continuously enhance the stability of expanded duplexes.
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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 | 0.000 |
| 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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".