Molecular Dynamics Simulations of Peptides from the Central Domain of Smooth Muscle Caldesmon
Bibliographic record
Abstract
The central domain of smooth muscle caldesmon contains a highly charged region consisting of ten 13-residue repeats. Experimental evidence obtained from the intact protein and fragments thereof suggests that this entire region forms a single stretch of stable alpha-helix. We have carried out molecular dynamics simulations on peptides consisting of one, two and three repeats to examine the mechanism of alpha-helical stability of the central domain at the atomic level. All three peptides show high helical stability on the timescale of the MD simulations. Deviations from alpha-helical structure in all the simulations arise mainly from the formation of long stretches of pi-helix. Interconversion between alpha-helical and pi-helical conformations occurs through insertion of water molecules into alpha-helical hydrogen bonds and subsequent formation of reverse turns. The alpha-helical structure is stabilized by electrostatic interactions (salt bridges) between oppositely charged sidechains with i,i+4 spacings, while the pi-helix is stabilized by i,i+5 salt bridge interactions. Possible i,i+3 salt bridges are of minor importance. There is a strong preference for salt bridges with a Glu residue N-terminal to a basic sidechain as compared to the opposite orientation. In the double and triple repeat peptides, strong i,i+4 salt bridges exist between the last Glu residue of one repeat and the first Lys residue of the next. This demonstrates a relationship between the repetitive nature of the central domain sequence and its ability to form very long stretches of alpha-helical structure.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".