Augmented and Programmatically Optimized LLM Prompts Reduce Chemical Hallucinations

Utilizing large Language models (LLMs) for handling scientific information comes with risk of the outputs not matching expectations, commonly called hallucinations. To fully utilize LLMs in research requires improving their accuracy, avoiding hallucinations, and extending their scope to research topics outside their direct training. There is also a benefit to getting the most accurate information from an LLM at the time of inference without having to create and train custom new models for each application. Here, augmented generation and machine learning-driven prompt optimization are combined to extract performance improvements over base LLM function on a common chemical research task. Specifically, an LLM was used to predict the topological polar surface area (TPSA) of molecules. By using augmented generation and machine learning-optimized prompts, the error in the prediction was reduced to 11.76 root-mean-squared error (RMSE) from 62.34 RMSE with direct calls to the same LLM.

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Publication Details

Journal
Journal of Chemical Information and Modeling
Published
2025-04-22
DOI
https://doi.org/10.1021/acs.jcim.4c02322
Citations
11
Primary Topic
Plant-based Medicinal Research
Type
article
Field-Weighted Citation Impact
17.13

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article

Augmented and Programmatically Optimized LLM Prompts Reduce Chemical Hallucinations

Scott M. Reed
11 citations
Journal of Chemical Information and Modeling
Plant-based Medicinal Research
17.13
article

Augmented and Programmatically Optimized LLM Prompts Reduce Chemical Hallucinations

Scott M. Reed
article en
11 citations

Abstract

Utilizing large Language models (LLMs) for handling scientific information comes with risk of the outputs not matching expectations, commonly called hallucinations. To fully utilize LLMs in research requires improving their accuracy, avoiding hallucinations, and extending their scope to research topics outside their direct training. There is also a benefit to getting the most accurate information from an LLM at the time of inference without having to create and train custom new models for each application. Here, augmented generation and machine learning-driven prompt optimization are combined to extract performance improvements over base LLM function on a common chemical research task. Specifically, an LLM was used to predict the topological polar surface area (TPSA) of molecules. By using augmented generation and machine learning-optimized prompts, the error in the prediction was reduced to 11.76 root-mean-squared error (RMSE) from 62.34 RMSE with direct calls to the same LLM.

Journal of Chemical Information and ModelingVol. 65(9)
University of Colorado Denver (US)
National Institute of General Medical Sciences
Zero hunger
Openalex Percentile: Top 1%
Plant-based Medicinal Research
17.13
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