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Foldseek is an ultra-fast structural alignment toolkit that encodes protein tertiary contacts as a 20-letter 3Di structural alphabet, then leverages MMseqs2 sequence-search machinery (k-mer prefilter + Smith-Waterman / TM-align) to search and cluster up to ~1000x faster than DALI/TM-align at near-identical sensitivity. Supports single-chain search/cluster, multi-chain (multimer) complex search/cluster, GPU acceleration on Ampere+ NVIDIA GPUs, and ProstT5-based search of FASTA queries against structure databases.