Computing, Analyzing, and Comparing the Radius of Gyration and Hydrodynamic Radius in Conformational Ensembles of Intrinsically Disordered Proteins

Mustapha Carab Ahmed; Ramon Crehuet; Kresten Lindorff-Larsen

doi:10.1007/978-1-0716-0524-0_21

Computing, Analyzing, and Comparing the Radius of Gyration and Hydrodynamic Radius in Conformational Ensembles of Intrinsically Disordered Proteins

Methods Mol Biol. 2020:2141:429-445. doi: 10.1007/978-1-0716-0524-0_21.

Authors

Mustapha Carab Ahmed¹, Ramon Crehuet^{1

2}, Kresten Lindorff-Larsen³

Affiliations

¹ Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen N, Denmark.
² Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.
³ Structural Biology and NMR Laboratory, Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen N, Denmark. [email protected].

PMID: 32696370
DOI: 10.1007/978-1-0716-0524-0_21

Abstract

The level of compaction of an intrinsically disordered protein may affect both its physical and biological properties, and can be probed via different types of biophysical experiments. Small-angle X-ray scattering (SAXS) probe the radius of gyration (R_g) whereas pulsed-field-gradient nuclear magnetic resonance (NMR) diffusion, fluorescence correlation spectroscopy, and dynamic light scattering experiments can be used to determine the hydrodynamic radius (R_h). Here we show how to calculate R_g and R_h from a computationally generated conformational ensemble of an intrinsically disordered protein. We further describe how to use a Bayesian/Maximum Entropy procedure to integrate data from SAXS and NMR diffusion experiments, so as to derive conformational ensembles in agreement with those experiments.

Keywords: Compaction; Conformational ensemble; Hydrodynamic radius; Intrinsically disordered protein; Radius of gyration.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Bayes Theorem
Cell Cycle Proteins / metabolism
Cyclin-Dependent Kinase Inhibitor Proteins / chemistry
Cyclin-Dependent Kinase Inhibitor Proteins / metabolism
Electrophoresis, Gel, Pulsed-Field
Entropy
F-Box Proteins / metabolism
Hydrodynamics
Hydrophobic and Hydrophilic Interactions
Intrinsically Disordered Proteins / chemistry*
Magnetic Resonance Imaging
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular / methods
Phosphorylation
Protein Conformation*
Protein Folding
Protein Processing, Post-Translational
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / metabolism
Scattering, Small Angle*
Spectrometry, Fluorescence
Static Electricity
Ubiquitin-Protein Ligases / metabolism
X-Ray Diffraction / methods*

Substances

CDC4 protein, S cerevisiae
Cell Cycle Proteins
Cyclin-Dependent Kinase Inhibitor Proteins
F-Box Proteins
Intrinsically Disordered Proteins
SIC1 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Ubiquitin-Protein Ligases