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Abstract The breakthrough in cryo-electron microscopy (cryo-EM) technology has led to an increasing number of density maps of biological macromolecules. However, constructing accurate protein complex atomic structures from cryo-EM maps remains a challenge. In this study, we extend our previously developed DEMO-EM to present DEMO-EM2, an automated method for constructing protein complex models from cryo-EM maps through an iterative assembly procedure intertwining chain- and domain-level matching and fitting for predicted chain models. The method was carefully evaluated on 27 cryo-electron tomography (cryo-ET) maps and 16 single-particle EM maps, where DEMO-EM2 models achieved an average TM-score of 0.92, outperforming those of state-of-the-art methods. The results demonstrate an efficient method that enables the rapid and reliable solution of challenging cryo-EM structure modeling problems.
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This content will become publicly available on July 12, 2025
Deep Learning Approach to Identify Protein’s Secondary Structure Elements
method for structure determination. Despite the substantial growth in deposited cryo-EM maps driven by advances in microscopy and image processing, accurately constructing models from these maps remains challenging. Extracting secondary structure information from EM maps is valuable for cryo-EM modeling. In this context, we introduce a novel deep learning secondary structure annotation framework specifically designed for intermediate-resolution cryo-EM maps, employing a three-dimensional Inception architecture. Testing it on diverse datasets, including maps with authentic intermediate resolutions, demonstrates its accuracy and robustness in identifying secondary structures in cryo-EM maps. We conducted a comparative analysis of our results against frameworks that exist in the state-of-the-art, and our framework demonstrated superior performance across nearly all secondary structure elements. We employed the F1 accuracy metric, yielding an average F1 score of 0.657 for helix, 0.712 for coil, and 0.596 for sheet predictions. Notably, certain helix and sheet predictions achieved an impressive F1 score of 0.881.
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- Award ID(s):
- 2153807
- PAR ID:
- 10541118
- Publisher / Repository:
- Springer, Singapore
- Date Published:
- Volume:
- 14954
- ISBN:
- 978-981-97-5128-0
- Subject(s) / Keyword(s):
- Protein Modeling Protein Secondary Structure Elements Deep Learning Cryo-EM Map Inception Architecture Machine Learning
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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