Molecular dynamics simulations reveal the impact of Ser295 phosphorylation on the structure of pyrin domain-containing NOD-like receptor 3
Bibliographic record
Abstract
jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf The nucleotide-binding, leucine rich repeat, and pyrin-containing 3 (NLRP3) protein is regulated by phosphorylation of Ser295 in the NACHT domain. This post-translational modification is known to inhibit the enzymatic ATPase activity of NLRP3 and impede inflammasome complex assembly. In this study, modeled structures of unphosphorylated and pSer295-phosphorylated NLRP3-DPYD were subjected to molecular dynamics simulations. The outputs showed Ser295 phosphorylation to induce topologic distention of subdomains that comprise the NACHT domain. The relative orientation of important residues within the nucleotide-binding domain (NBD) were altered. Notable structural changes were observed for important residues within the Walker B motif that immediately follow pSer295. A favorable electrostatic environment was created for two residues (Lys232 and His522) that interact with ADP. Several other basic residues could establish favourable charge-charge interactions with the dianionic phosphate of pSer295. Arg296 and Glu343 underwent a functional change from negative/stabilizing to positive/destabilizing interaction upon phosphorylation of Ser295. Taken together, the results suggest that local structural transformations within the NBD could have consequences on the catalytic efficiency of the enzyme and suppress nucleotide turnover.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".