Predicting structural and energetic changes in Met–aromatic motifs on methionine oxidation to the sulfoxide and sulfone
Bibliographic record
Abstract
Noncovalent interactions between Met and aromatic residues define a common Met-aromatic motif in proteins. Met oxidation to MetOn (n = 1 sulfoxide, n = 2 sulfone) alters protein stability and function. To predict the chemical and physical consequences of such oxidations, we modeled the chemistry and redox properties of MetOn-aromatic complexes in depth for comparison with our Met-aromatic models (E. A. Orabi and A. M. English, J. Phys. Chem. B, 2018, 122, 3760). We describe here ab initio quantum mechanical calculations at the MP2(full)/6-311++G(d,p) level of theory on complexes of MetOn (n = 1, 2; modeled by Me2SO and Me2SO2) with models of the side-chains of Phe (benzene, toluene), Trp (indole, 3-methylindole), Tyr (phenol, 4-methylphenol) and His (imidazole, 4-methylimidazole). Binding energies of the global minimum conformers (-3.4 to -11.9 kcal mol-1) indicate that the gas-phase Me2SOn-aromatics are 40-115% more stable than the Me2S-aromatics. Binding of S between the edge and face of the aromatic ring is favored in most complexes as it accommodates both robust σ- and π-type H-bonding. Interactions involving the σ-holes on the S atoms (σ-holeπar and σ-holeNar/Oar), as well as Sπ interactions in the sulfoxides, contribute to complex stability. Complexation modulates the ionization potential (IP) of the interacting fragments with the binding geometry dictating the center oxidized in the Me2SO-aromatics whereas the aromatic is oxidized in the Me2SO2 complexes because of the sulfone's high IP. Potentials of mean force reveal binding free energies of -0.2 to -0.7 kcal mol-1 in bulk water, which indicates that the Me2SOn-aromatics are up to 80% less stable than the corresponding aqueous Me2S-aromatics. Molecular dynamics simulations predict that Me2SOn preferentially interacts with the ring face and expose the dominance of π- vs. σ-type H-bonding in the hydrated complexes as found for the Me2S-aromatics. Our modeling will inform how Met/MetOn-aromatic motifs are determinants of redox-induced changes in proteins.
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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 | 0.000 |
| 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) | 0.001 | 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".