Static Recovery Is Not Dynamic Stability: Dynamics-Aware Benchmarking of Protein Motif Scaffolding
Only 8 of 55 statically solved protein-scaffold model–problem pairs passed every molecular-dynamics check.
The authors’ BILBY-MD framework compares designed scaffolds with reference simulations, checking structural drift, motif contacts and conformational energy landscapes. Of those 55 pairs, 31 met its MD-supported criterion; compact, self-contained motifs fared better than interface-like or context-dependent motifs. A separate benchmark, BILBY-PRO, covers 220 cases and tests six scaffold-generation models. RFDiffusion and Proteina solved more targets, while ESM3 generated more unique successful scaffolds on the targets it solved.
HF Daily Papers' note
The authors’ BILBY-MD framework compares designed scaffolds with reference simulations, checking structural drift, motif contacts and conformational energy landscapes. Of those 55 pairs, 31 met its MD-supported criterion; compact, self-contained motifs fared better than interface-like or context-dependent motifs. A separate benchmark, BILBY-PRO, covers 220 cases and tests six scaffold-generation models. RFDiffusion and Proteina solved more targets, while ESM3 generated more unique successful scaffolds on the targets it solved.
HF Daily Papers' note
score 4