Conformational ensembles of intrinsically disordered proteins and flexible multidomain proteins

被引:49
作者
Thomasen, F. Emil [1 ]
Lindorff-Larsen, Kresten [1 ]
机构
[1] Univ Copenhagen, Linderstrom Lang Ctr Prot Sci, Dept Biol, DK-2200 N Copenhagen N, Denmark
关键词
X-RAY-SCATTERING; PARAMAGNETIC RELAXATION ENHANCEMENT; SMALL-ANGLE SCATTERING; NITROXIDE SIDE-CHAIN; SINGLE-MOLECULE FRET; COARSE-GRAINED MODEL; FORCE-FIELD; NMR-RELAXATION; BIOLOGICAL MACROMOLECULES; STRUCTURAL ENSEMBLES;
D O I
10.1042/BST20210499
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:541 / 554
页数:14
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