https://3demmethods.i2pc.es/index.php?action=history&feed=atom&title=2025Zheng_Disorder 2026-05-24T21:06:56Z Revision history for this page on the wiki MediaWiki 1.44.2 https://3demmethods.i2pc.es/index.php?title=2025Zheng_Disorder&diff=5062&oldid=prev 2025-09-11T07:27:06Z

<p>Created page with &quot;== Citation == Zheng, S. 2025. Exploring the Bottleneck in Cryo-EM Dynamic Disorder Feature and Advanced Hybrid Prediction Model. Biophysica. 5, 3 (2025), 39. == Abstract == Cryo-electron microscopy single-particle analysis (cryo-EM SPA) has advanced threedimensional protein structure determination, yet resolving intrinsically disordered proteins and regions (IDPs/IDRs) remains challenging due to conformational heterogeneity. This research evaluates cryo-EM’s capaci...&quot;</p> <p><b>New page</b></p><div>== Citation ==<br /> <br /> Zheng, S. 2025. Exploring the Bottleneck in Cryo-EM Dynamic Disorder Feature and Advanced Hybrid Prediction Model. Biophysica. 5, 3 (2025), 39.<br /> <br /> == Abstract ==<br /> <br /> Cryo-electron microscopy single-particle analysis (cryo-EM SPA) has advanced threedimensional<br /> protein structure determination, yet resolving intrinsically disordered proteins<br /> and regions (IDPs/IDRs) remains challenging due to conformational heterogeneity. This<br /> research evaluates cryo-EM’s capacity to map dynamic regions, assesses the adaptability<br /> of disorder prediction tools, and explores optimization strategies for dynamic structure<br /> prediction. Cryo-EM SPA datasets from 2000 to 2024 were categorized into different periods,<br /> forming a database integrating sequence data and disorder indices. Established prediction<br /> tools—AlphaFold2 (pLDDT), flDPnn, and IUPred—were evaluated for transferability,<br /> while a multi-level CLTC hybrid model (combining CNN, LSTM, Transformer, and CRF<br /> architectures) was developed to link local conformational fluctuations with global sequence<br /> contexts. Analyses revealed consistent advancements in average resolution and model<br /> counts over the past decade, although mapping disordered regions remained technically<br /> demanding. Both the adapted AlphaFold pLDDT and the CLTC model demonstrated<br /> efficacy in predicting structurally variable and poorly resolved regions. A subset of the<br /> cryo-EM missing residues exhibited intermediate conformational features, suggesting classification<br /> ambiguities potentially influenced by experimental conditions. These findings<br /> systematically outline the evolving capabilities of cryo-EM in resolving dynamic regions,<br /> benchmark the adaptability of computational tools, and introduce a hybrid model to enhance<br /> prediction accuracy. This study provides a framework for addressing conformational<br /> heterogeneity, contributing to methodological advancements in structural biology.<br /> <br /> == Keywords ==<br /> <br /> == Links ==<br /> <br /> https://www.mdpi.com/2673-4125/5/3/39<br /> <br /> == Related software ==<br /> <br /> == Related methods ==<br /> <br /> == Comments ==</div>

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