# Language-Informed Flow Matching for Trend-Guided Structure-Based 3D Molecular Generation

arXiv: https://arxiv.org/abs/2608.31009 · HTML: https://mlsanity.com/paper/2608.31009/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 21 of its 34 references that are in the map.
- First posted on arXiv 31 Aug 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, 21 of 21)

- [FiLM: Visual Reasoning with a General Conditioning Layer](https://mlsanity.com/paper/1709.07871/) (2017)
- [Deep Sets](https://mlsanity.com/paper/1703.06114/) (2017)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Learning from Protein Structure with Geometric Vector Perceptrons](https://mlsanity.com/paper/2009.01411/) (2020)
- [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)
- [MolCA: Molecular Graph-Language Modeling with Cross-Modal Projector and Uni-Modal Adapter](https://mlsanity.com/paper/2310.12798/) (2023)
- [Training-Free Guidance Beyond Differentiability: Scalable Path Steering with Tree Search in Diffusion and Flow Models](https://mlsanity.com/paper/2502.11420/) (2025)
- [CBGBench: Fill in the Blank of Protein-Molecule Complex Binding Graph](https://mlsanity.com/paper/2406.10840/) (2024)
- [NExT-Mol: 3D Diffusion Meets 1D Language Modeling for 3D Molecule Generation](https://mlsanity.com/paper/2502.12638/) (2025)
- [Multi-domain Distribution Learning for De Novo Drug Design](https://mlsanity.com/paper/2508.17815/) (2025)
- [Chem3DLLM: 3D Multimodal Large Language Models for Chemistry](https://mlsanity.com/paper/2508.10696/) (2025)
- [Prior-Guided Flow Matching for Target-Aware Molecule Design with Learnable Atom Number](https://mlsanity.com/paper/2509.01486/) (2025)
- [MolGuidance: Advanced Guidance Strategies for Conditional Molecular Generation with Flow Matching](https://mlsanity.com/paper/2512.12198/) (2025)
- [Geometric Deep Learning for Structure-Based Drug Design: A Survey](https://mlsanity.com/paper/2306.11768/) (2023)
- [Controllable 3D Molecular Generation for Structure-Based Drug Design Through Bayesian Flow Networks and Gradient Integration](https://mlsanity.com/paper/2508.21468/) (2025)
- [Empowering LLMs for Structure-Based Drug Design via Exploration-Augmented Latent Inference](https://mlsanity.com/paper/2601.15333/) (2026)
- [MolSculpt: Sculpting 3D Molecular Geometries from Chemical Syntax](https://mlsanity.com/paper/2512.10991/) (2025)
- [Unveiling the Secret of AdaLN-Zero in Diffusion Transformer](https://mlsanity.com/paper/2608.09438/) (2026)

## Abstract (arXiv)

Structure-based drug design (SBDD) requires ligands that satisfy both 3D target affinity and 1D chemical validity. Existing controllable generation methods often rely on task-specific fine-tuning or externally imposed sampling-time guidance, adding cost and potentially conflicting with evolving 3D geometric constraints. We propose LiFT, a language-informed cross-modal framework built on Flow Matching for trend-guided 3D molecular generation across both de novo design and scaffold hopping. LiFT uses a "Sense-Evolve-Assemble" agent to generate target-aware SMILES as intermediate chemical conditions, from which a pre-trained chemical foundation model extracts continuous semantic priors. These priors are integrated into geometric generation through a lightweight semantic projector with zero-initialized adaptive normalization for stable cross-modal conditioning. We further introduce a Self-Conditioned Decoupled Router (SCDR), which modulates the velocity field according to intermediate structural states during ODE integration. Experiments on Cross-Docked2020 show that LiFT achieves competitive distribution matching while improving medicinal chemistry metrics and maintaining competitive structural validity under task-steering settings without additional generator fine-tuning. Our results suggest that language-derived chemical priors provide effective trend-level guidance for 3D molecular generation. Code and released artifacts are available at https://github.com/kasurl/LiFT.