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bioRxiv · 10.1101/2025.06.05.657588

SMART: An Integrated Platform Revolutionizing Cryo-Electron Microscopy Workflow from Data Acquisition to Atomic Modeling

Liu, H.·Wu, Y.·Zhang, W.·Xu, H.·Guo, Z.·Meng, F.·Men, X.·Guo, A. C.
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Abstract

Recent advancements in cryo-electron microscopy (cryo-EM) have revolutionized structural biology, yet persistent workflow fragmentation between data acquisition, reconstruction, and modeling limits its full potential. This paper presents SMART, the first fully integrated cryo-EM platform unifying three critical AI-driven modules: DataSmart (automated data collection), CryoSmart (3D reconstruction), and ModelSmart (end-to-end atomic modeling). The platform embeds more than 10 distinct AI algorithms across its workflow, achieving unprecedented automation levels. These advancements not only lower the expertise barrier for cryo-EM adoption but also establish a new paradigm for AI-empowered structural biology, with broad implications for high-throughput drug discovery. This protocol provides a comprehensive delineation of the operational procedures for the SMART platform. As an example, this protocol enabled the determination of the 2.1 [A] resolution structure of TRPML1, a Ca2+-permeable, nonselective, six-transmembrane tetrameric cation channel found in late endosomes and lysosomes (LELs) of mammalian cells. This integrated workflow enables users, including those with minimal cryo-EM experience, to efficiently complete the entire pipeline from data collection to atomic model building.

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Liu, H., Wu, Y., Zhang, W., Xu, H., Guo, Z., Meng, F., Men, X., Guo, A. C.. 2025-06-09. SMART: An Integrated Platform Revolutionizing Cryo-Electron Microscopy Workflow from Data Acquisition to Atomic Modeling. https://doi.org/10.1101/2025.06.05.657588

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