# HemePLM-Diffuse: A Scalable Generative Framework for Protein-Ligand Dynamics in Large Biomolecular System

arXiv: https://arxiv.org/abs/2508.16587 · HTML: https://mlsanity.com/paper/2508.16587/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 6 of its 16 references that are in the map.
- First posted on arXiv 7 Aug 2025.

## Builds on (most cited first, 6 of 6)

- [Tensor field networks: Rotation- and translation-equivariant neural networks for 3D point clouds](https://mlsanity.com/paper/1802.08219/) (2018)
- [SE(3)-Transformers: 3D Roto-Translation Equivariant Attention Networks](https://mlsanity.com/paper/2006.10503/) (2020)
- [SchNet: A continuous-filter convolutional neural network for modeling quantum interactions](https://mlsanity.com/paper/1706.08566/) (2017)
- [TorchMD-NET: Equivariant Transformers for Neural Network based Molecular Potentials](https://mlsanity.com/paper/2202.02541/) (2022)
- [EquiBind: Geometric Deep Learning for Drug Binding Structure Prediction](https://mlsanity.com/paper/2202.05146/) (2022)
- [GeoMol: Torsional Geometric Generation of Molecular 3D Conformer Ensembles](https://mlsanity.com/paper/2106.07802/) (2021)

## Abstract (arXiv)

Comprehending the long-timescale dynamics of protein-ligand complexes is very important for drug discovery and structural biology, but it continues to be computationally challenging for large biomolecular systems. We introduce HemePLM-Diffuse, an innovative generative transformer model that is designed for accurate simulation of protein-ligand trajectories, inpaints the missing ligand fragments, and sample transition paths in systems with more than 10,000 atoms. HemePLM-Diffuse has features of SE(3)-Invariant tokenization approach for proteins and ligands, that utilizes time-aware cross-attentional diffusion to effectively capture atomic motion. We also demonstrate its capabilities using the 3CQV HEME system, showing enhanced accuracy and scalability compared to leading models such as TorchMD-Net, MDGEN, and Uni-Mol.