Exploring the essential collective dynamics of interacting proteins: Application to prion protein dimers
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Bibliographic record
Abstract
Essential collective dynamics is a promising and robust approach for analysing the slow motions of macromolecules from short molecular dynamics trajectories. In this study, an extension of the method to treat a collection of interacting protein molecules is presented. The extension is applied to investigate the effects of dimerization on the collective dynamics of ovine prion protein molecules in two different arrangements. Examination of the structural plasticity shows that aggregation has a restricting effect on the local mobility of the prion protein molecules in the interfacial regions. Domain motions of the two dimeric ovine prion protein conformations are distinctly different and can be related to interatomic correlations at the interface. Correlated motions are among the slow collective modes extensively analysed by considering both main-chain and side-chain atoms. Correlation maps reveal the existence of a vast network of dynamically correlated side groups, which extends beyond individual subunits via interfacial interconnections. The network is formed by a core of hydrophobic side chains surrounded by hydrophilic groups at the periphery. The relevance of these findings are discussed in the context of mutations associated with prion diseases. The binding free energy of the dimeric conformations is evaluated to probe their thermodynamic stability. The descriptions afforded by the analysis of the essential collective dynamics of the prion dimers are consistent with their binding free energies. The agreement validates the extension of the methodology and provides a means of interpreting the collective dynamics in terms of the thermodynamic stability of ovine prion proteins.
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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