| title | TriGlue: a Biology-Inspired Generative Model for Generating Molecular Glue-Induced Ternary Complex |
|---|---|
| authors | Yuliang Yan, Shuo Yan, Haochun Tang, Yiqin Sun, Enyan Dai |
| date | 2026-08-04 |
| venue | arXiv (preprint, not peer reviewed) |
| id | arXiv:2607.22143 |
| upvotes | 2 (Hugging Face Daily Papers, 2026-11-01) |
| links | abs pdf hf code |
| abstract | 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. |
cite
@misc{yan2026triglue,
title={TriGlue: a Biology-Inspired Generative Model for Generating Molecular Glue-Induced Ternary Complex},
author={Yuliang Yan and Shuo Yan and Haochun Tang and Yiqin Sun and Enyan Dai},
year={2026},
eprint={2607.22143},
archivePrefix={arXiv},
url={https://arxiv.org/abs/2607.22143}
}