Determination of protein structural ensembles using cryo-electron microscopy

TL;DR

This paper reviews how cryo-electron microscopy combined with integrative methods can be used to determine comprehensive protein structural ensembles, capturing their dynamic behavior and conformational diversity.

Contribution

It provides an overview of current challenges, opportunities, and tools for integrating cryo-EM data with other sources to elucidate protein ensembles.

Findings

Cryo-EM is crucial for understanding protein disorder and dynamics.

Integrative approaches enhance structural ensemble determination.

The review highlights available computational tools for the community.

Abstract

Achieving a comprehensive understanding of the behaviour of proteins is greatly facilitated by the knowledge of their structures, thermodynamics and dynamics. All this information can be provided in an effective manner in terms of structural ensembles. A structural ensemble can be obtained by determining the structures, populations and interconversion rates for all the main states that a protein can occupy. To achieve this goal, integrative methods that combine experimental and computational approaches provide powerful tools. Here we focus on cryo-electron microscopy, which has become over recent years an invaluable resource to bridge the gap from order to disorder in structural biology. In this review, we provide a perspective of the current challenges and opportunities in determining protein structural ensembles using integrative approaches that can combine cryo-electron microscopy data with other available sources of information, along with an overview of the tools available to the community.