# CAGenMol: Condition-Aware Diffusion Language Model for Goal-Directed Molecular Generation

arXiv: https://arxiv.org/abs/2604.11483 · HTML: https://mlsanity.com/paper/2604.11483/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 22 of its 54 references that are in the map.
- First posted on arXiv 13 Apr 2026.

## Placed in

- Diffusion models / [Flow matching, time series and science](https://mlsanity.com/diffusion/flow-matching-time-series-and-science/)

## Builds on (most cited first, 22 of 22)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Proximal Policy Optimization Algorithms](https://mlsanity.com/paper/1707.06347/) (2017)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [Discrete Diffusion Modeling by Estimating the Ratios of the Data Distribution](https://mlsanity.com/paper/2310.16834/) (2023)
- [Simplified and Generalized Masked Diffusion for Discrete Data](https://mlsanity.com/paper/2406.04329/) (2024)
- [Therapeutics Data Commons: Machine Learning Datasets and Tasks for Drug Discovery and Development](https://mlsanity.com/paper/2102.09548/) (2021)
- [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)
- [A 3D Generative Model for Structure-Based Drug Design](https://mlsanity.com/paper/2203.10446/) (2022)
- [Generating 3D Molecules for Target Protein Binding](https://mlsanity.com/paper/2204.09410/) (2022)
- [DecompDiff: Diffusion Models with Decomposed Priors for Structure-Based Drug Design](https://mlsanity.com/paper/2403.07902/) (2024)
- [Differentiable Scaffolding Tree for Molecular Optimization](https://mlsanity.com/paper/2109.10469/) (2021)
- [GenMol: A Drug Discovery Generalist with Discrete Diffusion](https://mlsanity.com/paper/2501.06158/) (2025)
- [Gotta be SAFE: A New Framework for Molecular Design](https://mlsanity.com/paper/2310.10773/) (2023)
- [MolCRAFT: Structure-Based Drug Design in Continuous Parameter Space](https://mlsanity.com/paper/2404.12141/) (2024)
- [DecompOpt: Controllable and Decomposed Diffusion Models for Structure-based Molecular Optimization](https://mlsanity.com/paper/2403.13829/) (2024)
- [Zero-Shot 3D Drug Design by Sketching and Generating](https://mlsanity.com/paper/2209.13865/) (2022)
- [textttMiniMol: A Parameter-Efficient Foundation Model for Molecular Learning](https://mlsanity.com/paper/2404.14986/) (2024)
- [Taming Masked Diffusion Language Models via Consistency Trajectory Reinforcement Learning with Fewer Decoding Step](https://mlsanity.com/paper/2509.23924/) (2025)
- [Structure-based Drug Design Benchmark: Do 3D Methods Really Dominate?](https://mlsanity.com/paper/2406.03403/) (2024)
- [MolChord: Structure-Sequence Alignment for Protein-Guided Drug Design](https://mlsanity.com/paper/2510.27671/) (2025)

## Built on by (most cited first, 2 of 2)

- [On the Design Space of Discrete Diffusion Online Adaptation for Molecular Optimization](https://mlsanity.com/paper/2607.02834/) (2026)
- [One Sequence, Many Decodings: CAGenMol-2 Recasts Drug Design as Masked Molecular Inference](https://mlsanity.com/paper/2609.34301/) (2026)

## Abstract (arXiv)

Goal-directed molecular generation requires satisfying heterogeneous constraints such as protein--ligand compatibility and multi-objective drug-like properties, yet existing methods often optimize these constraints in isolation, failing to reconcile conflicting objectives (e.g., affinity vs. safety), and struggle to navigate the non-differentiable chemical space without compromising structural validity. To address these challenges, we propose CAGenMol, a condition-aware discrete diffusion framework over molecular sequences that formulates molecular design as conditional denoising guided by heterogeneous structural and property signals. By coupling discrete diffusion with reinforcement learning, the model aligns the generation trajectory with non-differentiable objectives while preserving chemical validity and diversity. The non-autoregressive nature of diffusion language model further enables iterative refinement of molecular fragments at inference time. Experiments on structure-conditioned, property-conditioned, and dual-conditioned benchmarks demonstrate consistent improvements over state-of-the-art methods in binding affinity, drug-likeness, and success rate, highlighting the effectiveness of our framework.