MolProphecy: Bridging Medicinal Chemists' Knowledge and Molecular Pre-Trained Models via a Multi-Modal Framework

Fuente: arXiv
Saved in:
Bibliographic Details
Main Authors: Zhao, Jianping, Zhou, Qiong, Wang, Tian, Fan, Yusi, Yang, Qian, Jiao, Li, Liu, Chang, Guo, Zhehao, Lu, Qi, Zhou, Fengfeng, Zhang, Ruochi
Format: Preprint
Published: 2025
Subjects:
Online Access:
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1866913926125453312
author Zhao, Jianping
Zhou, Qiong
Wang, Tian
Fan, Yusi
Yang, Qian
Jiao, Li
Liu, Chang
Guo, Zhehao
Lu, Qi
Zhou, Fengfeng
Zhang, Ruochi
author_facet Zhao, Jianping
Zhou, Qiong
Wang, Tian
Fan, Yusi
Yang, Qian
Jiao, Li
Liu, Chang
Guo, Zhehao
Lu, Qi
Zhou, Fengfeng
Zhang, Ruochi
contents MolProphecy is a human-in-the-loop (HITL) multi-modal framework designed to integrate chemists' domain knowledge into molecular property prediction models. While molecular pre-trained models have enabled significant gains in predictive accuracy, they often fail to capture the tacit, interpretive reasoning central to expert-driven molecular design. To address this, MolProphecy employs ChatGPT as a virtual chemist to simulate expert-level reasoning and decision-making. The generated chemist knowledge is embedded by the large language model (LLM) as a dedicated knowledge representation and then fused with graph-based molecular features through a gated cross-attention mechanism, enabling joint reasoning over human-derived and structural features. Evaluated on four benchmark datasets (FreeSolv, BACE, SIDER, and ClinTox), MolProphecy outperforms state-of-the-art (SOTA) models, achieving a 15.0 percent reduction in RMSE on FreeSolv and a 5.39 percent improvement in AUROC on BACE. Analysis reveals that chemist knowledge and structural features provide complementary contributions, improving both accuracy and interpretability. MolProphecy offers a practical and generalizable approach for collaborative drug discovery, with the flexibility to incorporate real chemist input in place of the current simulated proxy--without the need for model retraining. The implementation is publicly available at https://github.com/zhangruochi/MolProphecy.
format Preprint
id arxiv_https___arxiv_org_abs_2507_02932
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle MolProphecy: Bridging Medicinal Chemists' Knowledge and Molecular Pre-Trained Models via a Multi-Modal Framework
Zhao, Jianping
Zhou, Qiong
Wang, Tian
Fan, Yusi
Yang, Qian
Jiao, Li
Liu, Chang
Guo, Zhehao
Lu, Qi
Zhou, Fengfeng
Zhang, Ruochi
Machine Learning
Artificial Intelligence
Computational Engineering, Finance, and Science
MolProphecy is a human-in-the-loop (HITL) multi-modal framework designed to integrate chemists' domain knowledge into molecular property prediction models. While molecular pre-trained models have enabled significant gains in predictive accuracy, they often fail to capture the tacit, interpretive reasoning central to expert-driven molecular design. To address this, MolProphecy employs ChatGPT as a virtual chemist to simulate expert-level reasoning and decision-making. The generated chemist knowledge is embedded by the large language model (LLM) as a dedicated knowledge representation and then fused with graph-based molecular features through a gated cross-attention mechanism, enabling joint reasoning over human-derived and structural features. Evaluated on four benchmark datasets (FreeSolv, BACE, SIDER, and ClinTox), MolProphecy outperforms state-of-the-art (SOTA) models, achieving a 15.0 percent reduction in RMSE on FreeSolv and a 5.39 percent improvement in AUROC on BACE. Analysis reveals that chemist knowledge and structural features provide complementary contributions, improving both accuracy and interpretability. MolProphecy offers a practical and generalizable approach for collaborative drug discovery, with the flexibility to incorporate real chemist input in place of the current simulated proxy--without the need for model retraining. The implementation is publicly available at https://github.com/zhangruochi/MolProphecy.
title MolProphecy: Bridging Medicinal Chemists' Knowledge and Molecular Pre-Trained Models via a Multi-Modal Framework
topic Machine Learning
Artificial Intelligence
Computational Engineering, Finance, and Science
url https://arxiv.org/abs/2507.02932