Using Matched Molecular Series as a Predictive Tool To Optimize Biological Activity
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Bibliographic record
Abstract
A matched molecular series is the general form of a matched molecular pair and refers to a set of two or more molecules with the same scaffold but different R groups at the same position. We describe Matsy, a knowledge-based method that uses matched series to predict R groups likely to improve activity given an observed activity order for some R groups. We compare the Matsy predictions based on activity data from ChEMBLdb to the recommendations of the Topliss tree and carry out a large scale retrospective test to measure performance. We show that the basis for predictive success is preferred orders in matched series and that this preference is stronger for longer series. The Matsy algorithm allows medicinal chemists to integrate activity trends from diverse medicinal chemistry programs and apply them to problems of interest as a Topliss-like recommendation or as a hypothesis generator to aid compound design.
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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 | 0.001 | 0.001 |
| 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 | 0.001 | 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