Evolution of P450 Monooxygenases toward Formation of Transient Channels and Exclusion of Nonproductive Gases
Bibliographic record
Abstract
Gaseous molecules are essential for biological processes, yet mapping the migration of gas molecules into and out of proteins represents a significant challenge. Cytochrome P450 enzymes (P450s) contain numerous channels thought to be populated by their substrates, products, solvents, and gases, yet the principles underlying channel preference are unknown. We identified multiple putative ligand migration channels of two bacterial P450s, CYP102A1 (BM3) from Bacillus megaterium and CYP102A5 from Bacillus cereus, using implicit ligand sampling and free molecular dynamics simulations and furthermore characterized the energy of gas migration through each. We observed strong discrimination between preferred gas migration channels, previously identified substrate/product migration channels and water channels, and mapped putative O 2 reservoirs in the enzyme core. The protein backbone dynamics ( S 2 order parameter) unexpectedly revealed that some channels are transient in nature, with subchannels forming and merging and O 2 molecules hopping between subchannels. Finally, we present evidence of the evolution toward O 2 binding in conjunction with protection against inhibitory CO and exclusion of N 2 . Our results significantly enhance our understanding of gas migration in proteins and provide insights into the evolution of gas-utilizing enzymes.
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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".