Hydrophobic Protein−Ligand Interactions Preserved in the Gas Phase
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Bibliographic record
Abstract
The results of time-resolved thermal dissociation measurements and molecular dynamic simulations are reported for gaseous deprotonated ions of the specific complexes of bovine beta-lactoglobulin (Lg) and a series of the fatty acids (FA): CH(3)(CH(2))(x)COOH, where x = 10, 12, 14, and 16. At the reaction temperatures investigated, 25-66 degrees C, the gaseous ions dissociate exclusively by the loss of neutral FA. According to the kinetic data, and confirmed by ion mobility measurements, the (Lg + FA)(7-) ions exist in two, noninterconverting structures designated the fast (Lg + FA)(f)(7-) and slow (Lg + FA)(s)(7-) components. The Arrhenius parameters for both components are sensitive to the length of the FA aliphatic chain. For the fast components, the activation energy (E(a)) increases in a nearly linear fashion, with each methylene group contributing approximately 0.8 kcal mol(-1) to E(a). This is similar to the contribution of -CH(2)- groups to the solvation of n-alkanes in nonpolar solvents. Furthermore, the magnitude of the E(a) values for the fast components is similar to the solvation enthalpies expected for the FA aliphatic chains in nonpolar and weakly polar solvents. The E(a) values determined for the slow components are larger than those of the fast components. Furthermore, the E(a) values do not vary in a simple fashion with the length of the aliphatic chain. Molecular dynamics simulations performed on the (Lg + PA) complex revealed that, depending on the charge configuration, the (Lg + PA)(7-) ion can exist in two distinct structures, which differ primarily by the position of the EF loop. In the open structure the EF loop is positioned away from the entrance to the hydrophobic cavity and the ligand is stabilized only through nonpolar intermolecular interactions. In the closed structure the EF loop covers the entrance of the cavity and the carboxylic group of PA participates in H-bonds with residues on the EF loop or residues located at the entrance of the cavity. The loss of ligand from the closed structure would require both the cleavage of the H-bonds and the nonpolar contacts. Taken together, these results suggest that the aliphatic chain of the FA remains bound within the hydrophobic cavity in the gas phase (Lg + FA)(7-) ions. Furthermore, the barrier to dissociation of the (Lg + FA)(f)(7-) ions reflects predominantly the cleavage of the nonpolar intermolecular interactions, while for the (Lg + FA)(s)(7-) ions the FA is stabilized by both nonpolar interactions and H-bonds.
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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 it