LoL-align: sensitive and fast probabilistic protein structure alignment
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 α − C α distances. Here we show that LoL-align is markedly more sensitive in detecting remote homologs than TM-align and Dali on single- and multidomain benchmarks and achieves better alignment quality at 5–20 × their speed. LoL-align is fully integrated into Foldseek.
Authors
- Michel van Kempen (ORCID: https://orcid.org/0000-0002-2720-5714)
- Johannes Söding (ORCID: https://orcid.org/0000-0001-9642-8244)
- Cameron L. M. Gilchrist (ORCID: https://orcid.org/0000-0001-7798-427X)
- Milot Mirdita (ORCID: https://orcid.org/0000-0001-8637-6719)
- Lasse Reifenrath (ORCID: https://orcid.org/0009-0001-2925-7585)
- Martin Steinegger (ORCID: https://orcid.org/0000-0001-8781-9753)
- Gyuri Kim (ORCID: https://orcid.org/0000-0002-2242-2816)
- Soo Hyun Kim (ORCID: https://orcid.org/0000-0003-2131-5848)
- Mohammadreza Radnezhad (ORCID: https://orcid.org/0009-0005-1613-5537)
Institutions
- Seoul National University (KR)
- Korea Basic Science Institute (KR)
- Max Planck Institute for Multidisciplinary Sciences (DE)
- Campus-Institut Data Science (CIDAS) (DE)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Nature Methods
- Published
- 2026-10-14
- DOI
- https://doi.org/10.1038/s41592-026-03249-w
- Primary Topic
- Protein Structure and Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- Korea Basic Science Institute
- National Research Foundation of Korea
- Max-Planck-Gesellschaft
- Novo Nordisk
- Ministry of Science and ICT, South Korea