Constant-pH Molecular Dynamics Simulations Reveal a β-Rich Form of the Human Prion Protein

2010 ◽  
Vol 114 (39) ◽  
pp. 12692-12700 ◽  
Author(s):  
Sara R. R. Campos ◽  
Miguel Machuqueiro ◽  
António M. Baptista
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Prion Protein ◽  
Constant Ph ◽  
Human Prion Protein ◽  
Dynamics Simulations ◽  
Constant Ph Molecular Dynamics

scholarly journals Probing the Accuracy of Explicit Solvent Constant pH Molecular Dynamics Simulations for Peptides

2020 ◽  
Vol 16 (4) ◽  
pp. 2561-2569 ◽  
Author(s):  
Plamen Dobrev ◽  
Sahithya Phani Babu Vemulapalli ◽  
Nilamoni Nath ◽  
Christian Griesinger ◽  
Helmut Grubmüller
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Constant Ph ◽  
Explicit Solvent ◽  
Dynamics Simulations ◽  
Constant Ph Molecular Dynamics

scholarly journals Probing the Accuracy of Explicit Solvent Constant pH Molecular Dynamics Simulations for Peptides

2020 ◽  
Vol 118 (3) ◽  
pp. 140a
Author(s):  
Plamen N. Dobrev ◽  
Sahithya Vemulapalli ◽  
Nilamoni Nath ◽  
Christian Griesinger ◽  
Helmut Grubmueller
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Constant Ph ◽  
Explicit Solvent ◽  
Dynamics Simulations ◽  
Constant Ph Molecular Dynamics

scholarly journals Charge Interactions in a Highly Charge-depleted Protein

2020 ◽  
Author(s):  
Stefan Hervø-Hansen ◽  
Casper Højgaard ◽  
Kristoffer Enøe Johansson ◽  
Yong Wang ◽  
Khadija Wahni ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Nmr Spectroscopy ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Protein Electrostatics ◽  
Surface Charges ◽  
Constant Ph ◽  
Charged Residues ◽  
Dynamics Simulations ◽  
Constant Ph Molecular Dynamics

ABSTRACTInteractions between charged residues are difficult to study because of the complex network of interactions found in most proteins. We have designed a purposely simple system to investigate this problem by systematically introducing individual and pairs of charged and titratable residues in a protein otherwise free of such residues. We used constant pH molecular dynamics simulations, NMR spectroscopy, and thermodynamic double mutant cycles to probe the structure and energetics of the interaction between the charged residues. We found that the partial burial of surface charges contributes to a shift in pKa value, causing an aspartate to titrate in the neutral pH range. Additionally, the interaction between pairs of residues was found to be highly context dependent, with some pairs having no apparent preferential interaction, while other pairs would engage in coupled titration forming a highly stabilized salt bridge. We find good agreement between experiments and simulations, and use the simulations to rationalize our observations and to provide a detailed mechanistic understanding of the electrostatic interactions.SignificanceElectrostatic forces are important for protein folding and are favored targets of protein engineering. However, despite the many advances in the field of protein electrostatics, the prediction of changes in protein structure and function upon introduction or removal of titratable residues is still complicated. In order to provide a basic understanding of protein electrostatics we here characterize a highly charge-depleted protein and its titratable variants by a combination of NMR spectroscopy and constant pH molecular dynamics simulations. Our investigations reveal how strongly interacting residues engaged in salt bridging, can be characterized. Furthermore, our study may also enrich and facilitate the understanding of dehydration of salt-bridges and its potential effect on protein stability.

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