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

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Hauptverfasser: Malikussaid, Nuha, Hilal Hudan, Kurniawan, Isman
Format: Preprint
Veröffentlicht: 2025
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author Malikussaid
Nuha, Hilal Hudan
Kurniawan, Isman
author_facet Malikussaid
Nuha, Hilal Hudan
Kurniawan, Isman
contents Large Language Models demonstrate substantial promise for advancing scientific discovery, yet their deployment in disciplines demanding factual precision and specialized domain constraints presents significant challenges. Within molecular design for pharmaceutical development, these models can propose innovative molecular modifications but frequently generate chemically infeasible structures. We introduce VALID-Mol, a comprehensive framework that integrates chemical validation with LLM-driven molecular design, achieving an improvement in valid chemical structure generation from 3% to 83%. Our methodology synthesizes systematic prompt optimization, automated chemical verification, and domain-adapted fine-tuning to ensure dependable generation of synthesizable molecules with enhanced properties. Our contribution extends beyond implementation details to provide a transferable methodology for scientifically-constrained LLM applications with measurable reliability enhancements. Computational analyses indicate our framework generates promising synthesis candidates with up to 17-fold predicted improvements in target binding affinity while preserving synthetic feasibility.
format Preprint
id arxiv_https___arxiv_org_abs_2506_23339
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle VALID-Mol: a Systematic Framework for Validated LLM-Assisted Molecular Design
Malikussaid
Nuha, Hilal Hudan
Kurniawan, Isman
Machine Learning
Artificial Intelligence
Chemical Physics
Quantitative Methods
68T50 (Primary) 92E10, 68T07 (Secondary)
I.2.7; J.3; I.2.1; I.2.6
Large Language Models demonstrate substantial promise for advancing scientific discovery, yet their deployment in disciplines demanding factual precision and specialized domain constraints presents significant challenges. Within molecular design for pharmaceutical development, these models can propose innovative molecular modifications but frequently generate chemically infeasible structures. We introduce VALID-Mol, a comprehensive framework that integrates chemical validation with LLM-driven molecular design, achieving an improvement in valid chemical structure generation from 3% to 83%. Our methodology synthesizes systematic prompt optimization, automated chemical verification, and domain-adapted fine-tuning to ensure dependable generation of synthesizable molecules with enhanced properties. Our contribution extends beyond implementation details to provide a transferable methodology for scientifically-constrained LLM applications with measurable reliability enhancements. Computational analyses indicate our framework generates promising synthesis candidates with up to 17-fold predicted improvements in target binding affinity while preserving synthetic feasibility.
title VALID-Mol: a Systematic Framework for Validated LLM-Assisted Molecular Design
topic Machine Learning
Artificial Intelligence
Chemical Physics
Quantitative Methods
68T50 (Primary) 92E10, 68T07 (Secondary)
I.2.7; J.3; I.2.1; I.2.6
url https://arxiv.org/abs/2506.23339