Modelling conformational state dynamics and its role on infection for SARS-CoV-2 Spike protein variants
Why this work is in the frame
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Bibliographic record
Abstract
The SARS-CoV-2 Spike protein needs to be in an open-state conformation to interact with ACE2 to initiate viral entry. We utilise coarse-grained normal mode analysis to model the dynamics of Spike and calculate transition probabilities between states for 17081 variants including experimentally observed variants. Our results correctly model an increase in open-state occupancy for the more infectious D614G via an increase in flexibility of the closed-state and decrease of flexibility of the open-state. We predict the same effect for several mutations on glycine residues (404, 416, 504, 252) as well as residues K417, D467 and N501, including the N501Y mutation recently observed within the B.1.1.7, 501.V2 and P1 strains. This is, to our knowledge, the first use of normal mode analysis to model conformational state transitions and the effect of mutations on such transitions. The specific mutations of Spike identified here may guide future studies to increase our understanding of SARS-CoV-2 infection mechanisms and guide public health in their surveillance efforts.
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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 it