# Empirical Evidence for the Fragment level Understanding on Drug Molecular Structure of LLMs

arXiv: https://arxiv.org/abs/2401.07657 · HTML: https://mlsanity.com/paper/2401.07657/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 21 of its 49 references that are in the map.
- First posted on arXiv 15 Jan 2024.

## Builds on (most cited first, 21 of 21)

- [Training language models to follow instructions with human feedback](https://mlsanity.com/paper/2203.02155/) (2022)
- [Flow Network based Generative Models for Non-Iterative Diverse Candidate Generation](https://mlsanity.com/paper/2106.04399/) (2021)
- [Graph Convolutional Policy Network for Goal-Directed Molecular Graph Generation](https://mlsanity.com/paper/1806.02473/) (2018)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [Molecular De Novo Design through Deep Reinforcement Learning](https://mlsanity.com/paper/1704.07555/) (2017)
- [Hierarchical Generation of Molecular Graphs using Structural Motifs](https://mlsanity.com/paper/2002.03230/) (2020)
- [Optimization of Molecules via Deep Reinforcement Learning](https://mlsanity.com/paper/1810.08678/) (2018)
- [MoFlow: An Invertible Flow Model for Generating Molecular Graphs](https://mlsanity.com/paper/2006.10137/) (2020)
- [Deep Reinforcement Learning for De-Novo Drug Design](https://mlsanity.com/paper/1711.10907/) (2017)
- [Sample Efficiency Matters: A Benchmark for Practical Molecular Optimization](https://mlsanity.com/paper/2206.12411/) (2022)
- [Artificial Intelligence for Science in Quantum, Atomistic, and Continuum Systems](https://mlsanity.com/paper/2307.08423/) (2023)
- [Objective-Reinforced Generative Adversarial Networks (ORGAN) for Sequence Generation Models](https://mlsanity.com/paper/1705.10843/) (2017)
- [The Impact of Large Language Models on Scientific Discovery: a Preliminary Study using GPT-4](https://mlsanity.com/paper/2311.07361/) (2023)
- [Hit and Lead Discovery with Explorative RL and Fragment-based Molecule Generation](https://mlsanity.com/paper/2110.01219/) (2021)
- [MolGenSurvey: A Systematic Survey in Machine Learning Models for Molecule Design](https://mlsanity.com/paper/2203.14500/) (2022)
- [SMILES Enumeration as Data Augmentation for Neural Network Modeling of Molecules](https://mlsanity.com/paper/1703.07076/) (2017)
- [Learning To Navigate The Synthetically Accessible Chemical Space Using Reinforcement Learning](https://mlsanity.com/paper/2004.12485/) (2020)
- [Molecule Generation by Principal Subgraph Mining and Assembling](https://mlsanity.com/paper/2106.15098/) (2021)
- [De Novo Molecular Generation via Connection-aware Motif Mining](https://mlsanity.com/paper/2302.01129/) (2023)
- [De novo Drug Design using Reinforcement Learning with Multiple GPT Agents](https://mlsanity.com/paper/2401.06155/) (2023)
- [Probabilistic Generative Transformer Language models for Generative Design of Molecules](https://mlsanity.com/paper/2209.09406/) (2022)

## Abstract (arXiv)

AI for drug discovery has been a research hotspot in recent years, and SMILES-based language models has been increasingly applied in drug molecular design. However, no work has explored whether and how language models understand the chemical spatial structure from 1D sequences. In this work, we pre-train a transformer model on chemical language and fine-tune it toward drug design objectives, and investigate the correspondence between high-frequency SMILES substrings and molecular fragments. The results indicate that language models can understand chemical structures from the perspective of molecular fragments, and the structural knowledge learned through fine-tuning is reflected in the high-frequency SMILES substrings generated by the model.