Ab Initio Studies on the Mechanism of Tyrosine Coupling
Bibliographic record
Abstract
Oxidative stress is considered to be a major contributor to dysfunction in a host of disease states. Reactive oxygen species (ROS) mediate distinct oxidative alterations in biopolymers, including DNA, proteins, lipids, and lipoproteins. Currently, the mechanisms of biochemical reactions underlying oxidative stress are poorly understood because of the instability of ROS. One of the consequences of oxidative stress is one-electron oxidation of tyrosine (Tyr) residues in proteins, which represents a hallmark of this insult and is implicated in the pathogenesis of a number of pathological processes leading to atherosclerosis, inflammatory conditions, multiple system atrophy and several neurodegenerative diseases. Major products of oxidation of Tyr include protein-bound dityrosine and isodityrosine. In this report, the mechanism of tyrosine coupling (including structure and stability of a number of proposed reaction intermediates) is studied by high-level density functional and conventional ab initio methods including B3LYP, MP2, CASSCF, and CASPT2. It is demonstrated that dityrosine and isodityrosine are the most stable structures at all theoretical levels applied. In addition to classical structures of the reaction intermediates, evidence is found for a novel transient structure of Tyr dimer, stacked dityrosyl. This dimer is predicted to exist because of strong electron correlation between two tyrosyl moieties. The counterpoise corrected energy of stacked dityrosyl is below the energy of two tyrosyl radicals by about 95 kJ/mol at the PUMP2/6-31G** level. High proton affinity of tyrosyl radical (about 9.4 eV) suggests that positively charged amino acids in the vicinity of a solvent-exposed Tyr residue may increase the probability of tyrosine coupling.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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) | 0.000 | 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".