# AI-guided Antibiotic Discovery Pipeline from Target Selection to Compound Identification

arXiv: https://arxiv.org/abs/2504.11091 · HTML: https://mlsanity.com/paper/2504.11091/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 3 of its 34 references that are in the map.
- First posted on arXiv 15 Apr 2025.

## Builds on (most cited first, 3 of 3)

- [Structure-based Drug Design with Equivariant Diffusion Models](https://mlsanity.com/paper/2210.13695/) (2022)
- [Pocket2Mol: Efficient Molecular Sampling Based on 3D Protein Pockets](https://mlsanity.com/paper/2205.07249/) (2022)
- [3D Equivariant Diffusion for Target-Aware Molecule Generation and Affinity Prediction](https://mlsanity.com/paper/2303.03543/) (2023)

## Abstract (arXiv)

Antibiotic resistance presents a growing global health crisis, demanding new therapeutic strategies that target novel bacterial mechanisms. Recent advances in protein structure prediction and machine learning-driven molecule generation offer a promising opportunity to accelerate drug discovery. However, practical guidance on selecting and integrating these models into real-world pipelines remains limited. In this study, we develop an end-to-end, artificial intelligence-guided antibiotic discovery pipeline that spans target identification to compound realization. We leverage structure-based clustering across predicted proteomes of multiple pathogens to identify conserved, essential, and non-human-homologous targets. We then systematically evaluate six leading 3D-structure-aware generative modelsunicodex2014spanning diffusion, autoregressive, graph neural network, and language model architecturesunicodex2014on their usability, chemical validity, and biological relevance. Rigorous post-processing filters and commercial analogue searches reduce over 100 000 generated compounds to a focused, synthesizable set. Our results highlight DeepBlock and TamGen as top performers across diverse criteria, while also revealing critical trade-offs between model complexity, usability, and output quality. This work provides a comparative benchmark and blueprint for deploying artificial intelligence in early-stage antibiotic development.