Nature Communications (Jul 2024)

Accurate Prediction of Protein Structural Flexibility by Deep Learning Integrating Intricate Atomic Structures and Cryo-EM Density Information

  • Xintao Song,
  • Lei Bao,
  • Chenjie Feng,
  • Qiang Huang,
  • Fa Zhang,
  • Xin Gao,
  • Renmin Han

DOI
https://doi.org/10.1038/s41467-024-49858-x
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 14

Abstract

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Abstract The dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics.