Influence of electrostatic forces on the association kinetics and conformational ensemble of an intrinsically disordered protein

2020 ◽  
Vol 88 (12) ◽  
pp. 1607-1619 ◽  
Author(s):  
Erik C. Cook ◽  
Trevor P. Creamer
Keyword(s):  
Intrinsically Disordered Protein ◽  
Conformational Ensemble ◽  
Electrostatic Forces ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Association Kinetics

scholarly journals Computing, analyzing and comparing the radius of gyration and hydrodynamic radius in conformational ensembles of intrinsically disordered proteins

2019 ◽  
Author(s):  
Mustapha Carab Ahmed ◽  
Ramon Crehuet ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Hydrodynamic Radius ◽  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Radius Of Gyration ◽  
Conformational Ensemble ◽  
Conformational Ensembles ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Nmr Diffusion

AbstractThe 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 (Rg) 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 (Rh). Here we show how to calculate Rg and Rh 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.

scholarly journals A multiscale computational study of the conformation of the full-length intrinsically disordered protein MeCP2

2021 ◽  
Author(s):  
Cecilia Chavez-Garcia ◽  
Jerome Henin ◽  
Mikko Karttunen
Keyword(s):  
Experimental Data ◽  
Computational Study ◽  
Intrinsically Disordered Protein ◽  
Full Length ◽  
Conformational Space ◽  
Coarse Grained ◽  
Conformational Ensemble ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Coarse Grained Simulations

The malfunction of the Methyl CpG binding protein 2 (MeCP2) is associated to the Rett syndrome, one of the most common causes of cognitive impairment in females. MeCP2 is an intrinsically disordered protein (IDP), making its experimental characterization a challenge. There is currently no structure available for the full-length MeCP2 in any of the databases, and only the structure of its MBD domain has been solved. We used this structure to build a full-length model of MeCP2 by completing the rest of the protein via ab initio modelling. Using a combination of all-atom and coarse-grained simulations, we characterized its structure and dynamics as well as the conformational space sampled by the ID and TRD domains in the absence of the rest of the protein. The present work is the first computational study of the full-length protein. Two main conformations were sampled in the coarse-grained simulations: a globular structure similar to the one observed in the all-atom force field and a two-globule conformation. Our all-atom model is in good agreement with the available experimental data, predicting amino acid W104 to be buried, amino acids R111 and R133 to be solvent accessible, and having 4.1% of α-helix content, compared to the 4% found experimentally. Finally, we compared the model predicted by AlphaFold to our Modeller model. The model was not stable in water and underwent further folding. Together, these simulations provide a detailed (if perhaps incomplete) conformational ensemble of the full-length MeCP2, which is compatible with experimental data and can be the basis of further studies, e.g., on mutants of the protein or its interactions with its biological partners.

Self-Assembling Micelles Based on an Intrinsically Disordered Protein Domain

2018 ◽  
Author(s):  
Sarah Klass ◽  
Matthew J. Smith ◽  
Tahoe Fiala ◽  
Jessica Lee ◽  
Anthony Omole ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fusion Proteins ◽  
Organic Molecules ◽  
Intrinsically Disordered Protein ◽  
Protein Domain ◽  
Enzymatic Cleavage ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Self Assembling ◽  
Protein Tag

Herein, we describe a new series of fusion proteins that have been developed to self-assemble spontaneously into stable micelles that are 27 nm in diameter after enzymatic cleavage of a solubilizing protein tag. The sequences of the proteins are based on a human intrinsically disordered protein, which has been appended with a hydrophobic segment. The micelles were found to form across a broad range of pH, ionic strength, and temperature conditions, with critical micelle concentration (CMC) values below 1 µM being observed in some cases. The reported micelles were found to solubilize hydrophobic metal complexes and organic molecules, suggesting their potential suitability for catalysis and drug delivery applications.

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