Molecular Dynamics Based Predictions of the Structural and Functional Effects of Disease Causing Cardiac Troponin C Mutations
Bibliographic record
Abstract
Human cardiac troponin C (HcTnC), the regulatory calcium-binding component of the troponin complex, is responsible for the regulation of cardiac muscle contraction in response to varying cytosolic calcium levels. Mutations that are shown to increase the cTnC Ca2+ affinity are hypothesized to induce hypertrophic cardiomyopathies (HCM). Several mutations in HcTnC have been selected that are associated with HCM. These mutations include A8V, L29Q, C84Y, E134D, and D145E. The structural effects of these mutations have been modeled through equilibrium molecular dynamics and their functional and structural impacts have been assessed. In each mutant that was analyzed, the equilibrated structures have shown notable deviations from wild-type in the regions known to be cardiac troponin I (cTnI) interaction sites. There were differences in the conformation dynamics of site II and cTnC/cTnI interaction sites. We anticipate these correlations may contribute to Ca2+ affinity either directly or indirectly through cTnI association.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".