# PharMolixFM: All-Atom Foundation Models for Molecular Modeling and Generation

arXiv: https://arxiv.org/abs/2503.21788 · HTML: https://mlsanity.com/paper/2503.21788/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 37 of its 66 references that are in the map.
- First posted on arXiv 12 Mar 2025.

## Builds on (most cited first, 30 of 37)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [LLaMA: Open and Efficient Foundation Language Models](https://mlsanity.com/paper/2302.13971/) (2023)
- [DeepSeekMath: Pushing the Limits of Mathematical Reasoning in Open Language Models](https://mlsanity.com/paper/2402.03300/) (2024)
- [Segment Anything](https://mlsanity.com/paper/2304.02643/) (2023)
- [DeepSeek-R1: Incentivizing Reasoning Capability in LLMs via Reinforcement Learning](https://mlsanity.com/paper/2501.12948/) (2025)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Neural Discrete Representation Learning](https://mlsanity.com/paper/1711.00937/) (2017)
- [Improved Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2102.09672/) (2021)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [Swin Transformer V2: Scaling Up Capacity and Resolution](https://mlsanity.com/paper/2111.09883/) (2021)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Simple and Effective Masked Diffusion Language Models](https://mlsanity.com/paper/2406.07524/) (2024)
- [Florence: A New Foundation Model for Computer Vision](https://mlsanity.com/paper/2111.11432/) (2021)
- [Galactica: A Large Language Model for Science](https://mlsanity.com/paper/2211.09085/) (2022)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [A Comprehensive Survey on Pretrained Foundation Models: A History from BERT to ChatGPT](https://mlsanity.com/paper/2302.09419/) (2023)
- [DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking](https://mlsanity.com/paper/2210.01776/) (2022)
- [Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design](https://mlsanity.com/paper/2402.04997/) (2024)
- [Inference Scaling Laws: An Empirical Analysis of Compute-Optimal Inference for Problem-Solving with Language Models](https://mlsanity.com/paper/2408.00724/) (2024)
- [Geometric Latent Diffusion Models for 3D Molecule Generation](https://mlsanity.com/paper/2305.01140/) (2023)
- [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)
- [Symmetry-adapted generation of 3d point sets for the targeted discovery of molecules](https://mlsanity.com/paper/1906.00957/) (2019)
- [Mol-Instructions: A Large-Scale Biomolecular Instruction Dataset for Large Language Models](https://mlsanity.com/paper/2306.08018/) (2023)
- [DecompDiff: Diffusion Models with Decomposed Priors for Structure-Based Drug Design](https://mlsanity.com/paper/2403.07902/) (2024)
- [Conditional Antibody Design as 3D Equivariant Graph Translation](https://mlsanity.com/paper/2208.06073/) (2022)
- [DPLM-2: A Multimodal Diffusion Protein Language Model](https://mlsanity.com/paper/2410.13782/) (2024)
- [Bayesian Flow Networks](https://mlsanity.com/paper/2308.07037/) (2023)

## Abstract (arXiv)

Structural biology relies on accurate three-dimensional biomolecular structures to advance our understanding of biological functions, disease mechanisms, and therapeutics. While recent advances in deep learning have enabled the development of all-atom foundation models for molecular modeling and generation, existing approaches face challenges in generalization due to the multi-modal nature of atomic data and the lack of comprehensive analysis of training and sampling strategies. To address these limitations, we propose PharMolixFM, a unified framework for constructing all-atom foundation models based on multi-modal generative techniques. Our framework includes three variants using state-of-the-art multi-modal generative models. By formulating molecular tasks as a generalized denoising process with task-specific priors, PharMolixFM achieves robust performance across various structural biology applications. Experimental results demonstrate that PharMolixFM-Diff achieves competitive prediction accuracy in protein-small-molecule docking (83.9% vs. 90.2% RMSD < 2AA, given pocket) with significantly improved inference speed. Moreover, we explore the empirical inference scaling law by introducing more sampling repeats or steps. Our code and model are available at https://github.com/PharMolix/OpenBioMed.