Physics-inspired explainable AI for mechanistic and decision support in drug discovery

Explainable artificial intelligence (XAI) is increasingly recognized as essential for trustworthy drug discovery, yet many approaches remain post hoc and correlational. This review examines physics-inspired XAI as a framework for improving mechanistic interpretability and decision support at the molecular design stage. We highlight its strengths in modeling molecular recognition and local structure-property relations, while emphasizing that efficacy and toxicity emerge from biological and pharmacological processes beyond molecular physics. Current evidence suggests that explainability improves prioritization and experimental efficiency, although its impact on overall R&D outcomes remains limited. We propose 'Molecular Intelligence' as a decision-centric framework integrating prediction, validation and domain knowledge.

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Journal
Drug Discovery Today
Published
2026-04-21
DOI
https://doi.org/10.1016/j.drudis.2026.104679
Primary Topic
Computational Drug Discovery Methods
Type
article
Field-Weighted Citation Impact
0.00

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article

Physics-inspired explainable AI for mechanistic and decision support in drug discovery

Antonio Lavecchia
Drug Discovery Today
Computational Drug Discovery Methods
article

Physics-inspired explainable AI for mechanistic and decision support in drug discovery

Antonio Lavecchia
article en

Abstract

Explainable artificial intelligence (XAI) is increasingly recognized as essential for trustworthy drug discovery, yet many approaches remain post hoc and correlational. This review examines physics-inspired XAI as a framework for improving mechanistic interpretability and decision support at the molecular design stage. We highlight its strengths in modeling molecular recognition and local structure-property relations, while emphasizing that efficacy and toxicity emerge from biological and pharmacological processes beyond molecular physics. Current evidence suggests that explainability improves prioritization and experimental efficiency, although its impact on overall R&D outcomes remains limited. We propose 'Molecular Intelligence' as a decision-centric framework integrating prediction, validation and domain knowledge.

Drug Discovery TodayVol. 31(3)
Federico II University Hospital (IT), University of Naples Federico II (IT)
Ministero dell'Istruzione e del Merito
Openalex Percentile: Top 16%
Computational Drug Discovery Methods
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Physics-inspired explainable AI for mechanistic and decision support in drug discovery — Antonio Lavecchia · Drug Discovery Today (2026) | TGRS Research Map | TGRS