Transferred<sup>13</sup>C<i>T</i><sub>1</sub>Relaxation at Natural Isotopic Abundance: A Practical Method for Determining Site-Specific Changes in Ligand Flexibility upon Binding to a Macromolecule
Bibliographic record
Abstract
An NMR strategy is described for measuring changes in 13 C spin−lattice relaxation times ( T 1 ) of ligand molecules, at natural isotopic abundance, upon binding to macromolecules of potentially unlimited size. The rapidly reversible binding nature of a substrate-based inhibitor (BILN127SE, K i = 5.4 μM) with the NS3 protease domain of the hepatitis C virus has been well documented and has served as an appropriate system for testing the transferred 13 C T 1 concept. 13 C T 1 relaxation, which is sensitive to motions that occur on the pico- to nanosecond time scale, were first measured for free BILN127SE. Upon addition of the protease at a 25:1 inhibitor-to-protease ratio, differential changes in the 13 C T 1 relaxation times of BILN127SE were observed. The equilibrium binding nature of the complex, results in a transfer of T 1 relaxation information of the ligand from the bound to the free state where it is more easily detected. The relative changes in 13 C T 1 relaxation provides a qualitative insight into the site-specific changes in ligand immobilization upon binding to the protease. Comparisons of this dynamics information are made with structural data deduced from 1 H NOESY, line-broadening, J -coupling, and ROESY experiments. The combination of dynamics and structural information should provide medicinal chemists with further opportunities to design more potent, chemically rigidified inhibitors.
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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 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".