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Record W2978927798 · doi:10.1021/acsomega.9b01512

To Pass or Not To Pass: Predicting the Blood–Brain Barrier Permeability with the 3D-RISM-KH Molecular Solvation Theory

2019· article· en· W2978927798 on OpenAlex
Dipankar Roy, Vijaya Kumar Hinge, Andriy Kovalenko

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueACS Omega · 2019
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsNational Institute for NanotechnologyUniversity of Alberta
FundersNatural Sciences and Engineering Research Council of CanadaAlberta InnovatesCompute Canada
KeywordsSolvationWorkflowMolecular dynamicsMolecular descriptorChemistryPermeability (electromagnetism)Computer scienceArtificial intelligenceComputational chemistryQuantitative structure–activity relationshipBiological systemMoleculeStatistical physicsMachine learningPhysicsMembraneOrganic chemistry

Abstract

fetched live from OpenAlex

Predicting the ability of chemical species to cross the blood-brain barrier (BBB) is an active field of research for development and mechanistic understanding in the pharmaceutical industry. Here, we report the BBB permeability of a large data set of compounds by incorporating molecular solvation energy descriptors computed by the 3D-RISM-KH molecular solvation theory. We have been able to show, for the first time, that the computed excess chemical potential in different solvents can be successfully used to predict permeability of compounds in a binary manner (yes/no) via a minimum-descriptor-based model. Our findings successfully combine the molecular solvation theory with the machine learning approach to address one of the most daunting challenges in predictive structure-activity relationship modeling. The workflow presented in this work is simple enough to be used by nonexperts with ease.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.428
Threshold uncertainty score0.479

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0040.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.012
GPT teacher head0.277
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it