LoL-align: sensitive and fast probabilistic protein structure alignment.

LoL-align is significantly more sensitive than TM-align and Dali in detecting remote homologs, with 5-20 times faster alignment speed on benchmark datasets.

• Why it matters: Accurate and sensitive protein structure alignment is crucial for identifying distant evolutionary relationships that sequence-based methods may miss, improving functional annotation and understanding of protein families.
• What they did: The authors developed LoL-align, which maximizes a local log-odds score based on intra-protein Cα–Cα distances, and validated its performance on single- and multidomain benchmarks against existing tools.
• The result: LoL-align outperforms TM-align and Dali in sensitivity and alignment quality while maintaining a substantially faster speed, and is fully integrated into the Foldseek platform.