Coarse-grained modeling of the intrinsically disordered protein Histatin 5 in solution: Monte Carlo simulations in combination with SAXS

2016 ◽  
Vol 84 (6) ◽  
pp. 777-791 ◽  
Author(s):  
Carolina Cragnell ◽  
Dominique Durand ◽  
Bernard Cabane ◽  
Marie Skepö
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Intrinsically Disordered Protein ◽  
Coarse Grained ◽  
Histatin 5 ◽  
Intrinsically Disordered ◽  
Disordered Protein

A Coarse-Grained Molecular Dynamics Approach to the Study of the Intrinsically Disordered Protein α-Synuclein

2019 ◽  
Vol 59 (4) ◽  
pp. 1458-1471 ◽  
Author(s):  
Rafael Ramis ◽  
Joaquín Ortega-Castro ◽  
Rodrigo Casasnovas ◽  
Laura Mariño ◽  
Bartolomé Vilanova ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Intrinsically Disordered Protein ◽  
Coarse Grained ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Coarse Grained Molecular Dynamics

scholarly journals Glutenin and Gliadin, a Piece in the Puzzle of their Structural Properties in the Cell Described through Monte Carlo Simulations

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1095
Author(s):  
Joel Markgren ◽  
Mikael Hedenqvist ◽  
Faiza Rasheed ◽  
Marie Skepö ◽  
Eva Johansson
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Disulfide Bonds ◽  
Intrinsically Disordered Proteins ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Cysteine Residues ◽  
Chain Flexibility ◽  
Intrinsically Disordered ◽  
Intermolecular Disulfide Bonds

Gluten protein crosslinking is a predetermined process where specific intra- and intermolecular disulfide bonds differ depending on the protein and cysteine motif. In this article, all-atom Monte Carlo simulations were used to understand the formation of disulfide bonds in gliadins and low molecular weight glutenin subunits (LMW-GS). The two intrinsically disordered proteins appeared to contain mostly turns and loops and showed “self-avoiding walk” behavior in water. Cysteine residues involved in intramolecular disulfide bonds were located next to hydrophobic peptide sections in the primary sequence. Hydrophobicity of neighboring peptide sections, synthesis chronology, and amino acid chain flexibility were identified as important factors in securing the specificity of intramolecular disulfide bonds formed directly after synthesis. The two LMW-GS cysteine residues that form intermolecular disulfide bonds were positioned next to peptide sections of lower hydrophobicity, and these cysteine residues are more exposed to the cytosolic conditions, which influence the crosslinking behavior. In addition, coarse-grained Monte Carlo simulations revealed that the protein folding is independent of ionic strength. The potential molecular behavior associated with disulfide bonds, as reported here, increases the biological understanding of seed storage protein function and provides opportunities to tailor their functional properties for different applications.

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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