Computational close up on protein-protein interactions: how to unravel the invisible using molecular dynamics simulations?

2015 ◽  
Vol 5 (5) ◽  
pp. 345-359 ◽  
Author(s):  
Christin Rakers ◽  
Marcel Bermudez ◽  
Bettina G. Keller ◽  
Jérémie Mortier ◽  
Gerhard Wolber
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Dynamics Simulations ◽  
The Invisible

scholarly journals Polysorbate 80 Controls Morphology, Structure and Stability of Human Insulin Amyloid-Like Spherulites

2021 ◽  
Author(s):  
Xin Zhou ◽  
Dirk Fennema Galparsoro ◽  
Anders Oestergaard Madsen ◽  
Valeria Vetri ◽  
Marco van de Weert ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Human Insulin ◽  
Protein Interactions ◽  
Physicochemical Characteristics ◽  
Beta Sheets ◽  
Aggregation Kinetics ◽  
Polysorbate 80 ◽  
Protein Protein Interactions ◽  
Dynamics Simulations

Amyloid protein aggregates are not only associated with neurodegenerative diseases and may also occur as unwanted by-products in protein-based therapeutics. Surfactants are often employed to stabilize protein formulations and reduce the risk of aggregation. However, surfactants alter protein-protein interactions and may thus modulate the physicochemical characteristics of any aggregates formed. Human insulin aggregation was induced at low pH in the presence of varying concentrations of the surfactant polysorbate 80. Various spectroscopic and imaging methods were used to study the aggregation kinetics, as well as structure and morphology of the formed aggregates. Molecular dynamics simulations were employed to investigate the initial interaction between the surfactant and insulin. Addition of polysorbate 80 slowed down, but did not prevent, aggregation of insulin. Amyloid spherulites formed under all conditions, with a higher content of intermolecular beta-sheets in the presence of the surfactant above its critical micelle concentration. In addition, a denser packing was observed, leading to a more stable aggregate. Molecular dynamics simulations suggested a tendency for insulin to form dimers in the presence of the surfactant, indicating a change in protein-protein interactions. It is thus shown that surfactants not only alter aggregation kinetics, but also affect physicochemical properties of any aggregates formed.

scholarly journals Probing Polyoxometalate-Protein Interactions Using Molecular Dynamics Simulations

2016 ◽  
Vol 22 (43) ◽  
pp. 15280-15289 ◽  
Author(s):  
Albert Solé-Daura ◽  
Vincent Goovaerts ◽  
Karen Stroobants ◽  
Gregory Absillis ◽  
Pablo Jiménez-Lozano ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Protein Interactions ◽  
Dynamics Simulations

scholarly journals Molecular dynamics shows complex interplay and long-range effects of post-translational modifications in yeast protein interactions

2021 ◽  
Vol 17 (5) ◽  
pp. e1008988
Author(s):  
Nikolina ŠoŠtarić ◽  
Vera van Noort
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Protein Structures ◽  
Cellular Protein ◽  
Free Energy Calculations ◽  
Protein Protein Interactions ◽  
Post Translational Modifications ◽  
Protein Properties ◽  
Dynamics Simulations

Post-translational modifications (PTMs) play a vital, yet often overlooked role in the living cells through modulation of protein properties, such as localization and affinity towards their interactors, thereby enabling quick adaptation to changing environmental conditions. We have previously benchmarked a computational framework for the prediction of PTMs’ effects on the stability of protein-protein interactions, which has molecular dynamics simulations followed by free energy calculations at its core. In the present work, we apply this framework to publicly available data on Saccharomyces cerevisiae protein structures and PTM sites, identified in both normal and stress conditions. We predict proteome-wide effects of acetylations and phosphorylations on protein-protein interactions and find that acetylations more frequently have locally stabilizing roles in protein interactions, while the opposite is true for phosphorylations. However, the overall impact of PTMs on protein-protein interactions is more complex than a simple sum of local changes caused by the introduction of PTMs and adds to our understanding of PTM cross-talk. We further use the obtained data to calculate the conformational changes brought about by PTMs. Finally, conservation of the analyzed PTM residues in orthologues shows that some predictions for yeast proteins will be mirrored to other organisms, including human. This work, therefore, contributes to our overall understanding of the modulation of the cellular protein interaction networks in yeast and beyond.

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