Enhancing cryo-EM maps with 3D deep generative networks for assisting protein structure modeling

Bioinformatics. 2023 Aug 1;39(8):btad494. doi: 10.1093/bioinformatics/btad494.

Abstract

Motivation: The tertiary structures of an increasing number of biological macromolecules have been determined using cryo-electron microscopy (cryo-EM). However, there are still many cases where the resolution is not high enough to model the molecular structures with standard computational tools. If the resolution obtained is near the empirical borderline (3-4.5 Å), improvement in the map quality facilitates structure modeling.

Results: We report EM-GAN, a novel approach that modifies an input cryo-EM map to assist protein structure modeling. The method uses a 3D generative adversarial network (GAN) that has been trained on high- and low-resolution density maps to learn the density patterns, and modifies the input map to enhance its suitability for modeling. The method was tested extensively on a dataset of 65 EM maps in the resolution range of 3-6 Å and showed substantial improvements in structure modeling using popular protein structure modeling tools.

Availability and implementation: https://github.com/kiharalab/EM-GAN, Google Colab: https://tinyurl.com/3ccxpttx.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cryoelectron Microscopy
  • Models, Molecular
  • Protein Conformation
  • Proteins* / chemistry

Substances

  • Proteins