foldmason

name	foldmason
description	FoldMason — multiple protein structure alignment at scale (Steinegger lab). Use when: (1) Building structural MSAs from AFDB / predicted models, (2) Comparing folds across MAG protein families after Foldseek clustering, (3) Preparing structure-aware alignments for phylogeny or motif work. Upstream: https://github.com/steineggerlab/foldmason. Web: https://search.foldseek.com/foldmason. Route via homology-search.
license	MIT
category	analysis-tools
tags	["FoldMason","structure-MSA","Foldseek","alignment"]
upstream	https://github.com/steineggerlab/foldmason
stage	function

FoldMason

Upstream: steineggerlab/foldmason · Web: https://search.foldseek.com/foldmason

Citation

Gilchrist, C. L. M., Mirdita, M. & Steinegger, M. Multiple protein structure alignment at scale with FoldMason. Science 391, 485–488 (2026). https://doi.org/10.1126/science.ads6733

See also docs/references.md.

Analytical thinking

Foldseek finds pairwise structural neighbors; FoldMason builds scalable multiple structure alignments (FASTA + HTML reports). Useful after clustering dark proteins or AFDB hits into families.

vs	Prefer FoldMason when
foldseek	Need MSA of many structures, not just hit table
Sequence MSA (MAFFT/…)	Structures available / twilight zone
folddisco	Global structural MSA vs local motif

How to run

conda install -c bioconda foldmason
foldmason easy-msa structures/*.pdb result.fasta tmp --report-mode 1
# HTML report when --report-mode 1; webserver also available

Decision tree

Have a set of related structures?
├─ Pairwise search only → foldseek
├─ Multiple structure alignment → foldmason
├─ Short motif → folddisco
└─ Sequence MSA → hh-suite / classical aligners

Related skills

foldseek · folddisco · foldcomp · unicore · homology-search · phylogenomics · tool-selection