Integrating AlphaFold and deep learning for atomistic interpretation of cryo-EM maps

Journal Article · 17 November 2023 · Briefings in Bioinformatics

DOI: https://doi.org/10.1093/bib/bbad405 · OSTI ID:2217229

Dai, Xin; Wu, Longlong ; Yoo, Shinjae; Liu, Qun

Abstract Interpretation of cryo-electron microscopy (cryo-EM) maps requires building and fitting 3D atomic models of biological molecules. AlphaFold-predicted models generate initial 3D coordinates; however, model inaccuracy and conformational heterogeneity often necessitate labor-intensive manual model building and fitting into cryo-EM maps. In this work, we designed a protein model-building workflow, which combines a deep-learning cryo-EM map feature enhancement tool, CryoFEM (Cryo-EM Feature Enhancement Model) and AlphaFold. A benchmark test using 36 cryo-EM maps shows that CryoFEM achieves state-of-the-art performance in optimizing the Fourier Shell Correlations between the maps and the ground truth models. Furthermore, in a subset of 17 datasets where the initial AlphaFold predictions are less accurate, the workflow significantly improves their model accuracy. Our work demonstrates that the integration of modern deep learning image enhancement and AlphaFold may lead to automated model building and fitting for the atomistic interpretation of cryo-EM maps.

• Research Organization: Brookhaven National Laboratory (BNL), Upton, NY (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER)
• Grant/Contract Number: SC0012704
• OSTI ID: 2217229
• Report Number(s): BNL-224938-2023-JAAM; bbad405
• Journal Information: Briefings in Bioinformatics, Journal Name: Briefings in Bioinformatics Journal Issue: 6 Vol. 24; ISSN 1467-5463
• Publisher: Oxford University PressCopyright Statement
• Country of Publication: United Kingdom
• Language: English