Artificial Intelligence Advances for De Novo Molecular Structure Modeling in Cryo-EM

TL;DR

This paper reviews recent advances in AI, especially deep learning, for de novo molecular structure modeling in cryo-EM, highlighting its potential to revolutionize biomedical research.

Contribution

It systematically reviews ML/DL-based methods for cryo-EM de novo modeling and discusses their significance and future directions.

Findings

Deep learning methods outperform traditional approaches in cryo-EM modeling.

AI techniques significantly reduce manual effort and increase accuracy.

The field shows great potential for biomedical applications.

Abstract

Cryo-electron microscopy (cryo-EM) has become a major experimental technique to determine the structures of large protein complexes and molecular assemblies, as evidenced by the 2017 Nobel Prize. Although cryo-EM has been drastically improved to generate high-resolution three-dimensional (3D) maps that contain detailed structural information about macromolecules, the computational methods for using the data to automatically build structure models are lagging far behind. The traditional cryo-EM model building approach is template-based homology modeling. Manual de novo modeling is very time-consuming when no template model is found in the database. In recent years, de novo cryo-EM modeling using machine learning (ML) and deep learning (DL) has ranked among the top-performing methods in macromolecular structure modeling. Deep-learning-based de novo cryo-EM modeling is an important application of artificial intelligence, with impressive results and great potential for the next generation of molecular biomedicine. Accordingly, we systematically review the representative ML/DL-based de novo cryo-EM modeling methods. And their significances are discussed from both practical and methodological viewpoints. We also briefly describe the background of cryo-EM data processing workflow. Overall, this review provides an introductory guide to modern research on artificial intelligence (AI) for de novo molecular structure modeling and future directions in this emerging field.