Bridging the Gap between Differential Mobility, Log <i>S</i>, and Log <i>P</i> Using Machine Learning and SHAP Analysis
Bibliographic record
Abstract
Aqueous solubility, log S, and the water–octanol partition coefficient, log P, are physicochemical properties that are used to screen the viability of drug candidates and to estimate mass transport in the environment. In this work, differential mobility spectrometry (DMS) experiments performed in microsolvating environments are used to train machine learning (ML) frameworks that predict the log S and log P of various molecule classes. In lieu of a consistent source of experimentally measured log S and log P values, the OPERA package was used to evaluate the aqueous solubility and hydrophobicity of 333 analytes. With ion mobility/DMS data ( e.g., CCS, dispersion curves) as input, we used ML regressors and ensemble stacking to derive relationships with a high degree of explainability, as assessed via SHapley Additive exPlanations (SHAP) analysis. The DMS-based regression models returned scores of R 2 = 0.67 and RMSE = 1.03 ± 0.10 for log S predictions and R 2 = 0.67 and RMSE = 1.20 ± 0.10 for log P after 5-fold random cross-validation. SHAP analysis reveals that the regressors strongly weighted gas-phase clustering in log P correlations. The addition of structural descriptors ( e.g., # of aromatic carbons) improved log S predictions to yield RMSE = 0.84 ± 0.07 and R 2 = 0.78. Similarly, log P predictions using the same data resulted in an RMSE of 0.83 ± 0.04 and R 2 = 0.84. The SHAP analysis of log P models highlights the need for additional experimental parameters describing hydrophobic interactions. These results were achieved with a smaller dataset (333 instances) and minimal structural correlation compared to purely structure-based models, underscoring the value of employing DMS data in predictive models.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".