Computational insight into hydrogen persulfide and a new additive model for chemical and biological simulations
Bibliographic record
Abstract
S-Sulfhydration of cysteine to the Cys-SSH persulfide is an oxidative post-translational modification that plays an important regulatory role in many physiological systems. Though hydrogen persulfide (H2S2) has recently been established as a signaling and cellular sulfhydration reagent, the chemistry and chemical biology of persulfides remain poorly explored. We first report an extensive high-level ab initio quantum chemical investigation of (H2S2)n, (H2S2)m·H2O, and (H2O)m·H2S2 clusters (n = 1-3 and m = 1, 2) and of H2S2 complexes with 19 compounds that model the side chains of naturally-occurring amino acids. The high polarizability of S necessitates the use of large, very diffuse, basis sets for proper description of H2S2 and its complexes. H2S2 possesses a skewed equilibrium geometry, with nonpolar trans and more polar cis conformers 6 and 8 kcal mol-1 higher in energy, respectively; the skewed conformation is preserved in all neutral and cationic complexes while a cis geometry prevails in some anionic complexes. H2S2 is found to be a better H-bond donor and a poorer acceptor than H2S, and that in complexes with H2O, alcohols and amines, H2S2 is a better H-bond donor. Radical delocalization on both S atoms stabilizes the perthiyl (HSS˙) over the thiyl (HS˙) radical and results in a ∼20 kcal mol-1 lower S-H homolytic bond dissociation in H2S2, making it a potential antioxidant. A simple additive model is optimized for H2S2 and used together with the TIP3P model and the CHARMM36 all-atom force field (FF) to investigate the structure and thermodynamic properties of liquid H2S2 and the solubility of H2S2 in water, and to model H2S2-protein interactions (for which new FF parameters are further developed). Very weak H-bonding characterizes liquid H2S2 and it is found immiscible in liquid water with a trend in H-bonding strengths between H2S2 and H2O in the order O-HO ≫ S-HO > O-HS. This work does not only provide a thorough description of the structure and energetics of H2S2 and its various complexes, but also yields a reliable FF for investigating H2S2 in chemistry and biology.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".