Bibliographic record
Abstract
This study deals with thermodynamic characterization of the role of water in drug-DNA and protein-DNA recognition. To this end, we have employed volumetric, calorimetric, and spectroscopic measurements to study the binding of an intercalator (ethidium bromide), a minor groove binder (Hoechst 33258), and a repressor (cro protein) to various DNA structures. A common feature of these reactions is the large number of water molecules that are released to the bulk upon the binding. Specifically, ethidium association with poly(rA)poly(rU), poly(dAdT)poly(dAdT), poly(dGdC)poly(dGdC), poly(dIdC)poly(dldC), and poly(rU)poly(rA)poly(rU) is accompanied by a net release of 11+/-3, 23.5+/-3, 18+/-3, 18+/-3, and 3.5+/-4.5 water molecules per binding site, respectively. Hoechst 33258 association with d(CGCGAATTCGCG)2, poly(dAdT)poly(dAdT), and poly(dA)poly(dT) results in release of 55+/-8, 54+/-5, and 63+/-4 waters to the bulk, respectively. Cro binding to its consensus operator DNA induces a release of approximately 800 waters from both their hydration. The thermodynamic contribution of dehydration is highly favorable being, in absolute magnitude, on the order or higher than the net binding free energy. Conformational contributions to the free energy are also evaluated in all binding events. Our results suggest that, for the reactions of intercalation and cro binding, the favorable contribution of hydration changes is nearly offset by an unfavorable change in configurational entropy of the reacting molecules. A large decrease in configurational entropy of cro protein and its operator DNA is consistent with significant conformational changes of these molecules accompanying their association. The binding-induced structural perturbations of cro and the related increase in its rigidity are reflected in a dramatic 45% decrease in the intrinsic coefficient of adiabatic compressibility of the protein. In general, our results emphasize the significant role of water in determining the specificity and affinity of DNA recognition and the need for expanding such studies to further characterize the structural and thermodynamic contributions of hydration in important biochemical reactions.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".