# Prompt Engineering for Transformer-based Chemical Similarity Search Identifies Structurally Distinct Functional Analogues

arXiv: https://arxiv.org/abs/2305.16330 · HTML: https://mlsanity.com/paper/2305.16330/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 8 of its 46 references that are in the map.
- First posted on arXiv 17 May 2023.

## Builds on (most cited first, 8 of 8)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Emergent Abilities of Large Language Models](https://mlsanity.com/paper/2206.07682/) (2022)
- [Language Models are Multilingual Chain-of-Thought Reasoners](https://mlsanity.com/paper/2210.03057/) (2022)
- [ChemBERTa: Large-Scale Self-Supervised Pretraining for Molecular Property Prediction](https://mlsanity.com/paper/2010.09885/) (2020)
- [Large-Scale Chemical Language Representations Capture Molecular Structure and Properties](https://mlsanity.com/paper/2106.09553/) (2021)
- [The Synthesizability of Molecules Proposed by Generative Models](https://mlsanity.com/paper/2002.07007/) (2020)
- [Keeping it Simple: Language Models can learn Complex Molecular Distributions](https://mlsanity.com/paper/2112.03041/) (2021)

## Abstract (arXiv)

Chemical similarity searches are widely used in-silico methods for identifying new drug-like molecules. These methods have historically relied on structure-based comparisons to compute molecular similarity. Here, we use a chemical language model to create a vector-based chemical search. We extend implementations by creating a prompt engineering strategy that utilizes two different chemical string representation algorithms: one for the query and the other for the database. We explore this method by reviewing the search results from five drug-like query molecules (penicillin G, nirmatrelvir, zidovudine, lysergic acid diethylamide, and fentanyl) and three dye-like query molecules (acid blue 25, avobenzone, and 2-diphenylaminocarbazole). We find that this novel method identifies molecules that are functionally similar to the query, indicated by the associated patent literature, and that many of these molecules are structurally distinct from the query, making them unlikely to be found with traditional chemical similarity search methods. This method may aid in the discovery of novel structural classes of molecules that achieve target functionality.