# MotifBench: A standardized protein design benchmark for motif-scaffolding problems

arXiv: https://arxiv.org/abs/2502.12479 · HTML: https://mlsanity.com/paper/2502.12479/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 9 of its 46 references that are in the map.
- First posted on arXiv 18 Feb 2025.

## Builds on (most cited first, 9 of 9)

- [Diffusion probabilistic modeling of protein backbones in 3D for the motif-scaffolding problem](https://mlsanity.com/paper/2206.04119/) (2022)
- [Practical and Asymptotically Exact Conditional Sampling in Diffusion Models](https://mlsanity.com/paper/2306.17775/) (2023)
- [SE(3) diffusion model with application to protein backbone generation](https://mlsanity.com/paper/2302.02277/) (2023)
- [DPLM-2: A Multimodal Diffusion Protein Language Model](https://mlsanity.com/paper/2410.13782/) (2024)
- [Improved motif-scaffolding with SE(3) flow matching](https://mlsanity.com/paper/2401.04082/) (2024)
- [Out of Many, One: Designing and Scaffolding Proteins at the Scale of the Structural Universe with Genie 2](https://mlsanity.com/paper/2405.15489/) (2024)
- [A framework for conditional diffusion modelling with applications in motif scaffolding for protein design](https://mlsanity.com/paper/2312.09236/) (2023)
- [On diffusion posterior sampling via sequential Monte Carlo for zero-shot scaffolding of protein motifs](https://mlsanity.com/paper/2412.05788/) (2024)
- [Joint Design of Protein Sequence and Structure based on Motifs](https://mlsanity.com/paper/2310.02546/) (2023)

## Built on by (most cited first, 2 of 2)

- [Unlocking Multimodal Protein Language Models at Inference Time](https://mlsanity.com/paper/2608.25855/) (2026)
- [Valid Stopping in Adaptive Generator-Verifier Loops](https://mlsanity.com/paper/2610.06432/) (2026)

## Abstract (arXiv)

The motif-scaffolding problem is a central task in computational protein design: Given the coordinates of atoms in a geometry chosen to confer a desired biochemical function (a motif), the task is to identify diverse protein structures (scaffolds) that include the motif and maintain its geometry. Significant recent progress on motif-scaffolding has been made due to computational evaluation with reliable protein structure prediction and fixed-backbone sequence design methods. However, significant variability in evaluation strategies across publications has hindered comparability of results, challenged reproducibility, and impeded robust progress. In response we introduce MotifBench, comprising (1) a precisely specified pipeline and evaluation metrics, (2) a collection of 30 benchmark problems, and (3) an implementation of this benchmark and leaderboard at github.com/blt2114/MotifBench. The MotifBench test cases are more difficult compared to earlier benchmarks, and include protein design problems for which solutions are known but on which, to the best of our knowledge, state-of-the-art methods fail to identify any solution.