MELD-Adapt: On-the-Fly Belief Updating in Integrative Molecular Dynamics
Bibliographic record
Abstract
Integrative structural biology synergizes experimental data with computational methods to elucidate the structures and interactions within biomolecules, a task that becomes critical in the absence of high-resolution structural data. A challenging step for integrating the data is knowing the expected accuracy or belief in the dataset. We previously showed that the Modeling Employing Limited Data (MELD) approach succeeds at predicting structures and finding the best interpretation of the data when the initial belief is equal to or slightly lower than the real value. However, the initial belief might be unknown to the user, as it depends on both the technique and the system of study. Here we introduce MELD-Adapt, designed to dynamically evaluate and infer the reliability of input data while at the same time finding the best interpretation of the data and the structures compatible with it. We demonstrate the utility of this method across different systems, particularly emphasizing its capability to correct initial assumptions and identify the correct fraction of data to produce reliable structural models. The approach is tested with two benchmark sets: the folding of 12 proteins with coarse physical insights and the binding of peptides with varying affinities to the extraterminal domain using chemical shift perturbation data. We find that subtle differences in data structure (e.g., locally clustered or globally distributed), starting belief, and force field preferences can have an impact on the predictions, limiting the possibility of a transferable protocol across all systems and data types. Nonetheless, we find a wide range of initial setup conditions that will lead to successful sampling and identification of native states, leading to a robust pipeline. Furthermore, disagreements about how much data is enforced and satisfied rapidly serve to identify incorrect setup conditions.
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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 | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 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".