MotifBench: A standardized protein design benchmark for motif-scaffolding problems
This addresses reproducibility and comparability issues for researchers in computational protein design, though it is incremental as it builds on existing evaluation methods.
The authors tackled the lack of standardized evaluation in protein design for motif-scaffolding problems by introducing MotifBench, a benchmark with 30 test cases, precise metrics, and a leaderboard, which includes difficult problems where state-of-the-art methods currently fail.
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.