LoL-align: sensitive and fast probabilistic protein structure alignment

Reifenrath, L.; van Kempen, M.; Kim, G.; Kim, S. H.; Radnezhad, M.; Mirdita, M.; Steinegger, M.; Söding, J.

doi:10.1101/2025.11.24.690091

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bioRxiv · 10.1101/2025.11.24.690091

LoL-align: sensitive and fast probabilistic protein structure alignment

Reifenrath, L.·van Kempen, M.·Kim, G.·Kim, S. H.·Radnezhad, M.·Mirdita, M.·Steinegger, M.·Söding, J.

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Abstract

The ubiquitous availability of protein structures permits replacing sequence alignment with more accurate and sensitive structure alignment algorithms. LoL-align maximizes a local log-odds score for proteins to be homologous, given their intra-protein C - C distances. LoL-align is markedly more sensitive in detecting remote homologs than TMalign and DALI on single- and multi-domain benchmarks and achieves better alignment quality at 5-20x their speed. LoL-align is fully integrated into Foldseek.

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Reifenrath, L., van Kempen, M., Kim, G., Kim, S. H., Radnezhad, M., Mirdita, M., Steinegger, M., Söding, J.. 2025-11-25. LoL-align: sensitive and fast probabilistic protein structure alignment. https://doi.org/10.1101/2025.11.24.690091

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