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Record W4416527189 · doi:10.1101/2025.11.20.689585

The Human-In-the-Loop Drug Design Framework with Equivariant Rectified Flow

2025· preprint· W4416527189 on OpenAlexaff
Yung‐Fu Huang, Xingang Peng, Q. Xu, Xingchao Liu, Yijie Wang, Qiang Liu, Jian Peng, Jianzhu Ma

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Language
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsTellabs (Canada)
Fundersnot available
KeywordsInterface (matter)Generative grammarInformation flowFlow (mathematics)Equivariant map

Abstract

fetched live from OpenAlex

Abstract Advancements in AI-based drug design often face obstacles due to incomplete datasets, hindering progress to clinical trials. Human experts bring invaluable expertise and nuanced contextual understanding to drug design. There are two main difficulties in integrating human knowledge into the drug development process. First, human annotations are costly, and traditional machine learning algorithms require a large number of samples to be effective. Second, human experts are unable to accurately describe their expertise using natural language, nor can they precisely specify what kind of molecule is needed before seeing the generated molecules. To address these problems, we propose a new platform, called HIL-DD, for experts to infuse their experience by selecting molecules generated by AI that meet their criteria, or discarding those that do not. The core generative technology utilizes an Equivariant Rectified Flow Model (ERFM), which offers faster generation speeds than conventional diffusion models, enabling efficient human-AI collaboration. More importantly, we provide a user-friendly interface to ensure smooth and effective collaboration between human experts and AI systems. Rigorous experiments demonstrate that our system can produce 3D molecules that align with expert expectations in minimal interactive sessions. These generated molecules maintain drug-like qualities comparable to those created by current state-of-the-art models.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.006
Threshold uncertainty score0.021

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0010.002
Scholarly communication0.0010.001
Open science0.0030.002
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0060.001

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.

Opus teacher head0.032
GPT teacher head0.280
Teacher spread0.248 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreMethods

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".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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