VALID-Mol: a Systematic Framework for Validated LLM-Assisted Molecular Design

• URL: http://arxiv.org/abs/2506.23339v1
• Date: Sun, 29 Jun 2025 17:17:04 GMT
• Title: VALID-Mol: a Systematic Framework for Validated LLM-Assisted Molecular Design
• Authors: Malikussaid, Hilal Hudan Nuha,
• Abstract summary: We present VALID-Mol, a framework for integrating chemical validation with Large Language Models (LLMs)<n>Our approach combines methodical prompt engineering, automated chemical validation, and a fine-tuned domain-adapted LLM to ensure reliable generation of synthesizable molecules.
• Score: 0.0
• License: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Abstract: Large Language Models (LLMs) demonstrate remarkable potential for scientific discovery, but their application in domains requiring factual accuracy and domain-specific constraints remains challenging. In molecular design for drug discovery, LLMs can suggest creative molecular modifications but often produce chemically invalid or impractical structures. We present VALID-Mol, a systematic framework for integrating chemical validation with LLM-driven molecular design that increases the rate of generating valid chemical structures from 3% to 83%. Our approach combines methodical prompt engineering, automated chemical validation, and a fine-tuned domain-adapted LLM to ensure reliable generation of synthesizable molecules with improved properties. Beyond the specific implementation, we contribute a generalizable methodology for scientifically-constrained LLM applications, with quantifiable reliability improvements. Computational predictions suggest our framework can generate promising candidates for synthesis with up to 17-fold computationally predicted improvements in target affinity while maintaining synthetic accessibility. We provide a detailed analysis of our prompt engineering process, validation architecture, and fine-tuning approach, offering a reproducible blueprint for applying LLMs to other scientific domains where domain-specific validation is essential.

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