Abstract
Accurate prediction of protein structures is essential for understanding biological functions and guiding biomedical research. However, maintaining synchronization between structure models and rapidly expanding, continuously evolving protein sequence databases remains a major challenge. Here, we present AlphaSync (alphasync.stjude.org), a comprehensive resource that complements the AlphaFold Protein Structure Database. AlphaSync currently provides 2.6 million UniProt-synchronized structural models, including predictions for 40,016 updated proteins and isoforms from 925 species. AlphaSync achieves complete, up-to-date proteome coverage for 42 species, including humans, key pathogens and model organisms. It also provides residue-level annotations such as solvent accessibility, dihedral angles, intrinsic disorder status and over 4.7 billion atom-level noncovalent contacts. Its up-to-date structural models and detailed annotations will facilitate the study of protein structure–function relationships, assessment of sequence variants and machine learning tasks including protein design. With an intuitive web interface and application programming interface, AlphaSync enables protein research at scale and in detail.
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Data availability
Newly predicted updated structures for the latest UniProt release can be obtained online (https://alphasync.stjude.org/download under a CC BY 4.0 license). Also available for download are PAE scores and the exact AlphaFold parameters used to predict structures. AlphaSync’s residue-level data can be programmatically retrieved through the AlphaSync API (https://alphasync.stjude.org/api).
Code availability
AlphaSync’s source code is available from GitHub (https://github.com/langbnj/alphasync) under a BSD-3-Clause license. The website code is available upon request.
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Acknowledgements
We thank I. Chen, M. Phelps and D. Malinverni for their helpful input, C. Burdyshaw for help deploying AlphaFold and other members of the M.M.B. group for their helpful input and discussions. We acknowledge and thank the American Lebanese Syrian Associated Charities for financial support. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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Contributions
B.L. conceptualized, built and implemented the project and wrote the manuscript. B.M. created the algorithm to predict disordered residues using AlphaFold-derived calculations and provided unpublished code and implementation examples for the disorder predictor feature. B.I.S. created the Lahuta Python package for the analysis of noncovalent interactions and protein contacts, provided access to the unpublished software for the intraprotein contact calculation feature and is helping to maintain the database. J.P. helped implement the Mol* protein structure viewer and PAE visualization. M.M.B. oversaw the project and provided guidance on the writing and editing of the manuscript.
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Nature Structural & Molecular Biology thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editors: Sara Osman and Melina Casadio, in collaboration with the Nature Structural & Molecular Biology team.
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Supplementary information
Supplementary Table 1
Species included in AlphaSync and their degree of completion. This table shows the 925 species with structures available in AlphaSync, as well as the number of structures available and those still missing from its complete reviewed and canonical reference proteome. It also clearly marks the 48 model organisms and global health proteomes selected in the AFDB that we prioritized, as well as the 42 fully completed species (including isoforms) in AlphaSync.
Supplementary Table 2
AlphaFold 2 parameters used for structure prediction. This table shows an overview of the parameters, software and database versions used for AlphaFold 2 structure prediction in AlphaSync.
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Lang, B., Mészáros, B., Sejdiu, B.I. et al. AlphaSync is an enhanced AlphaFold structure database synchronized with UniProt. Nat Struct Mol Biol 32, 2628–2632 (2025). https://doi.org/10.1038/s41594-025-01719-x
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DOI: https://doi.org/10.1038/s41594-025-01719-x
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