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

TL;DR

MotifBench provides a standardized, challenging benchmark for protein motif-scaffolding, enabling consistent evaluation and comparison of computational methods in this crucial area of protein design.

Contribution

It introduces a comprehensive benchmark with a pipeline, metrics, and 30 problems to improve evaluation consistency and progress in motif-scaffolding research.

Findings

Benchmark problems are more difficult than previous ones.

State-of-the-art methods often fail to find solutions on these problems.

Provides a publicly available leaderboard for ongoing evaluation.

Abstract

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.