Intrinsically disordered proteins (IDPs) and multidomain proteins with flexible linkers show a high level of structural heterogeneity and are best described by ensembles consisting of multiple conformations with associated thermodynamic weights. Determining conformational ensembles usually involves the integration of biophysical experiments and computational models. In this review, we discuss current approaches to determine conformational ensembles of IDPs and multidomain proteins, including the choice of biophysical experiments, computational models used to sample protein conformations, models to calculate experimental observables from protein structure, and methods to refine ensembles against experimental data. We also provide examples of recent applications of integrative conformational ensemble determination to study IDPs and multidomain proteins and suggest future directions for research in the field.
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February 2022
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Cover Image
Cover Image
The highly conserved enzyme IMPDH plays an essential role in purine biosynthesis and is tightly regulated by many different mechanisms. Depicted here are cryo-EM structures of the large retinal splice variant of IMPDH1 in different filament assembly conformations overlaid on a cryo-EM micrograph of IMPDH1 filaments. Cover artwork created by Jesse Hansen.
Review Article|
February 07 2022
Conformational ensembles of intrinsically disordered proteins and flexible multidomain proteins
F. Emil Thomasen;
F. Emil Thomasen
Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark
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Kresten Lindorff-Larsen
e-mail: lindorff@bio.ku.dk
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Publisher: Portland Press Ltd
Received:
December 10 2021
Revision Received:
January 13 2022
Accepted:
January 17 2022
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem Soc Trans (2022) 50 (1): 541–554.
Article history
Received:
December 10 2021
Revision Received:
January 13 2022
Accepted:
January 17 2022
Citation
F. Emil Thomasen, Kresten Lindorff-Larsen; Conformational ensembles of intrinsically disordered proteins and flexible multidomain proteins. Biochem Soc Trans 28 February 2022; 50 (1): 541–554. doi: https://doi.org/10.1042/BST20210499
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