# TriGlue: a Biology-Inspired Generative Model for Generating Molecular Glue-Induced Ternary Complex

arXiv: https://arxiv.org/abs/2607.22143 · HTML: https://mlsanity.com/paper/2607.22143/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 19 of its 61 references that are in the map.
- First posted on arXiv 24 Jul 2026.

## Builds on (most cited first, 19 of 19)

- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Scaling Rectified Flow Transformers for High-Resolution Image Synthesis](https://mlsanity.com/paper/2403.03206/) (2024)
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- [Movie Gen: A Cast of Media Foundation Models](https://mlsanity.com/paper/2410.13720/) (2024)
- [Flow Matching on General Geometries](https://mlsanity.com/paper/2302.03660/) (2023)
- [SE(3) diffusion model with application to protein backbone generation](https://mlsanity.com/paper/2302.02277/) (2023)
- [3D Equivariant Diffusion for Target-Aware Molecule Generation and Affinity Prediction](https://mlsanity.com/paper/2303.03543/) (2023)
- [SE(3)-Stochastic Flow Matching for Protein Backbone Generation](https://mlsanity.com/paper/2310.02391/) (2023)
- [A 3D Generative Model for Structure-Based Drug Design](https://mlsanity.com/paper/2203.10446/) (2022)
- [Dirichlet Flow Matching with Applications to DNA Sequence Design](https://mlsanity.com/paper/2402.05841/) (2024)
- [DecompDiff: Diffusion Models with Decomposed Priors for Structure-Based Drug Design](https://mlsanity.com/paper/2403.07902/) (2024)
- [Independent SE(3)-Equivariant Models for End-to-End Rigid Protein Docking](https://mlsanity.com/paper/2111.07786/) (2021)
- [Full-Atom Peptide Design based on Multi-modal Flow Matching](https://mlsanity.com/paper/2406.00735/) (2024)
- [PPFlow: Target-aware Peptide Design with Torsional Flow Matching](https://mlsanity.com/paper/2405.06642/) (2024)
- [DiffDock-PP: Rigid Protein-Protein Docking with Diffusion Models](https://mlsanity.com/paper/2304.03889/) (2023)
- [Unified Guidance for Geometry-Conditioned Molecular Generation](https://mlsanity.com/paper/2501.02526/) (2025)
- [SE(3)-Equivariant Ternary Complex Prediction Towards Target Protein Degradation](https://mlsanity.com/paper/2502.18875/) (2025)

## Abstract (arXiv)

Molecular glue degraders have emerged as a promising strategy for targeted protein degradation by inducing ternary complex formation between an E3 ubiquitin ligase and a target protein. Despite their therapeutic potential, computational design of molecular glues remains largely unexplored. Unlike conventional structure-based drug design, molecular glue design is governed by the unknown protein-protein interface and requires the simultaneous modeling of ligand generation, protein-protein docking, and ternary complex assembly. In this work, we formulate molecular glue design as a ternary complex generation problem and propose a biology-inspired generative framework, TriGlue. Motivated by the mechanism of molecular glue action, we decompose ternary complex generation into two coupled stages: interface estimation and interface-conditioned complex generation. First, we develop an SE(3)-equivariant interface estimation module that predicts a geometrically constrained protein-protein interface from unbound monomer structures. Second, we introduce an interface-conditioned ternary flow matching network that jointly generates the molecular glue and predicts the rigid-body transformation required to assemble the ternary complex. Extensive experiments demonstrate that TriGlue generates chemically valid molecules and produces plausible ternary complexes, which highlight the potential of biology-inspired generative modeling for accelerating molecular glue discovery. Our code is available at https://github.com/yuliangyan0807/molecular-glue-design.