Multiple protein structure alignment at scale with FoldMason

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Source: Science Magazine

Original: https://www.science.org/doi/abs/10.1126/science.ads6733?af=R...

Published: 2026-01-29T07:00:02Z

FoldMason is a progressive multiple protein structure alignment (MSTA) method that uses structural alphabets from the Foldseek tool to align hundreds of thousands of protein structures.[1][2][3] Protein structure is conserved even outside of sequence, making MSTA essential for the analysis of distantly related proteins.[1][2][3] The method outperformed the alignment quality of the current best methods and is two orders of magnitude faster than other MSTA tools.[1][2][3] FoldMason calculates confidence scores, offers interactive visualizations, and provides the speed and accuracy needed for large-scale protein structure analyzes in the era of precise structure prediction.[1][2][3] On the glycoproteins of the Flaviviridae family, he demonstrates how his MSTAs support phylogenetic analysis under the so-called twilight zone.[1][2][3] FoldMason is freely available open-source software at foldmason.foldseek.com and web server search.foldseek.com/foldmason.[1][2][3]