Computational Studies of Cu(II)/Met and Cu(I)/Met Binding Motifs Relevant for the Chemistry of Alzheimer's Disease
Bibliographic record
Abstract
A systematic study of the binding motifs of Cu(II) and Cu(I) to a methionine model peptide, namely, N-formylmethioninamide 1, has been carried out by quantum chemical computations. Geometries of the coordination modes obtained at the B3LYP/6-31G(d) level of theory are discussed in the context of copper coordination by the peptide backbone and the S atom of a methionine residue in peptides with special emphasis on Met35 of the amyloid-beta peptide (Abeta) of Alzheimer's disease. The relative binding free energies in the gas phase, DeltaG(g), are calculated at the B3LYP/6-311+G(2df,2p)//B3LYP/6-31G(d) level of theory, and the solvation affects are included by means of the COSMO model to obtain the relative binding energies in solution, DeltaG(aq). A free energy of binding, DeltaG(aq) = -19.4 kJ mol(-1), relative to aqueous Cu(II) and the free peptide is found for the most stable Cu(II)/Met complex, 12. The most stable Cu(I)/Met complex, 23, is bound by -15.6 kJ mol(-1) relative to the separated species. The reduction potential relative to the standard hydrogen electrode is estimated to be E degrees (12/23) = 0.41 V. On the basis of these results, the participation of Met35 as a low affinity binding site of Cu(II) in Abeta, and its role in the redox chemistry underlying Alzheimer's disease is discussed.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| 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".