Fast and accurate multiple-protein-sequence alignment at scale with FAMSA2.

We introduce FAMSA2, an algorithm that produces high-accuracy multiple-protein-sequence alignments at high speed. Across structural, phylogenetic and functional benchmarks, FAMSA2 matches or exceeds the accuracy of state-of-the-art tools while running 400 times faster on average than existing aligners. By combining progressive alignment with medoid clustering-based guide tree construction and a dissimilarity measure derived from the longest common subsequence, it enables scalable alignment of massive protein families.