The Binding of Fe(II)–Heme to the Amyloid Beta Peptide of Alzheimer’s Disease: QM/MM Investigations
Bibliographic record
Abstract
The structures of complexes between Aβ(1-42) and ferroheme (Fe(II)-heme) were determined by application of Amber and ONIOM(B3LYP/6-31G(d):Amber) methodology. Attachment at each of the three His residues was investigated. In each case, direct bonding of the iron to the His residue is augmented by the formation of secondary salt bridges between the carboxylate groups of the heme and positively charged residues of Aβ (at His13, by Lys16 and the N-terminus; at His14, by both Lys16 and Lys28; at His6, by Arg5) or by H-bonding and hydrophobic interactions (at His6, by Asp7 or Phe20). The results indicate a slight preference for His13 followed by His6 and His14, with the lowest eight structures lying within 36 kJ mol(-1) of each other. The methodology is not precise enough to permit a definitive statement as to the relative stabilities, nor to the absolute binding affinities, which are predicted to be less than 70 kJ mol(-1). The results bear on the question of how heme and copper may bind simultaneously to Aβ. They confirm that the reduced species can bind independently, Cu(+) at His13-His14 and Fe(II)-heme at His6.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".