OVO, an open-source ecosystem for de novo protein design

OVO (pronounced "oh-voh") consolidates models, workflows, data management, and interactive visualization into a scalable, high-performance, infrastructure-agnostic platform for de novo protein design. OVO features Nextflow-based workflow orchestration, a storage layer, and both command-line and web interfaces that democratize scaffold design, binder design and diversification, and validation workflows.

Ovo, an Open-Source Ecosystem for De Novo Protein Design, David Prihoda, Marco Ancona, Tereza Calounova, Adam Kral, Lukas Polak, Hugo Hrban, Nicholas J. Dickens, Danny Asher Bitton bioRxiv 2025.11.27.691041; doi: https://doi.org/10.1101/2025.11.27.691041

🐣 Getting started

To get started with OVO, please refer to the User Guide.

To preview the OVO web app (without the ability to submit jobs), see the OVO Demo Server.

▶️ Demo video

https://github.com/user-attachments/assets/7b339fa6-c6de-467d-90d0-5cd15f83c498

🧬 Methods & Acknowledgments

We gratefully acknowledge the authors and developers of the following methods and tools available from OVO:

Method Name	Description	Reference / Paper	Link
RFdiffusion	Diffusion-based protein structure generation	Watson et al. 2023	GitHub
RFdiffusion3	Design of all-atom biomolecular interactions	Butcher et al. 2025	GitHub
ProteinMPNN	Protein sequence design for fixed backbones	Dauparas et al. 2022	GitHub
LigandMPNN	Atomic context-conditioned protein sequence design	Dauparas et al. 2025	GitHub
PyRosetta FastRelax	Binder sequence design protocol	Bennett et al. 2023	GitHub
AlphaFold2 / ColabDesign	Deep learning-based protein structure prediction	Jumper et al. 2021	GitHub (AlphaFold2), GitHub (ColabDesign)
BindCraft	Binder design using AF2 backpropagation	Pacesa et al. 2024	GitHub
Boltz	Deep learning-based protein structure prediction	Wohlwend et al. 2024, Passaro et al. 2025	GitHub
ESM-1v	Protein language model for variant effect	Meier et al. 2021	GitHub
ESM-IF	Inverse folding with protein language models	Hsu et al. 2022	GitHub
DSSP	Secondary structure assignment	Kabsch & Sander 1983, Joosten et al. 2010	GitHub
PEP-Patch	Protein surface patches analysis	Kufareva et al. 2023	GitHub
Protein-Sol	Protein solubility prediction	Hebditch et al. 2017	Web

🛠️ Development

OVO is an open-source project and we welcome contributions from the community.

Please refer to the Developer Guide for information on how to contribute to OVO.