Structure-based drug design (SBDD) focuses on designing small-molecule ligands that bind to specific protein pockets. Computational methods are integral in modern SBDD workflows and often make use of virtual screening methods via docking or pharmacophore search. Modern generative modeling approaches have focused on improving novel ligand discovery by enabling de novo design. In this work, we recognize that these tasks share a common structure and can therefore be represented as different instantiations of a consistent generative modeling framework. We propose a unified approach in OMTRA, a multi-modal flow matching model that flexibly performs many tasks relevant to SBDD, including some with no analogue in conventional workflows. Additionally, we curate a dataset of 500M 3D molecular conformers, complementing protein-ligand data and expanding the chemical diversity available for training. OMTRA obtains state of the art performance on pocket-conditioned de novo design and docking; however, the effects of large-scale pretraining and multi-task training are modest. All code, trained models, and dataset for reproducing this work are available at https://github.com/gnina/OMTRA
@article{arxiv.2512.05080,
title = {OMTRA: A Multi-Task Generative Model for Structure-Based Drug Design},
author = {Ian Dunn and Liv Toft and Tyler Katz and Juhi Gupta and Riya Shah and Ramith Hettiarachchi and David R. Koes},
journal= {arXiv preprint arXiv:2512.05080},
year = {2025}
}
Comments
Presented at the Machine Learning for Structural Biology Workshop, 2025