2023Beton Fitting

Citation

J. G. Beton, T. Cragnolini, M. Kaleel, T. Mulvaney, A. Sweeney, and M. Topf, “Integrating model simulation tools and cryo-electron microscopy,” Wiley Interdisciplinary Reviews: Computational Molecular Science, vol. 13, no. 3, p. e1642, 2023.

Abstract

The power of computer simulations, including machine-learning, has become an inseparable part of scientific analysis of biological data. This has significantly impacted the field of cryogenic electron microscopy (cryo-EM), which has grown dramatically since the “resolution-revolution.” Many maps are now solved at 3–4 Å or better resolution, although a significant proportion of maps deposited in the Electron Microscopy Data Bank are still at lower resolution, where the positions of atoms cannot be determined unambiguously. Additionally, cryo-EM maps are often characterized by a varying local resolution, partly due to conformational heterogeneity of the imaged molecule. To address such problems, many computational methods have been developed for cryo-EM map reconstruction and atomistic model building. Here, we review the development in algorithms and tools for building models in cryo-EM maps at different resolutions. We describe methods for model building, including rigid and flexible fitting of known models, model validation, small-molecule fitting, and model visualization. We provide examples of how these methods have been used to elucidate the structure and function of dynamic macromolecular machines.

Links

https://wires.onlinelibrary.wiley.com/doi/full/10.1002/wcms.1642