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Gas Phase Protein Folding Triggered by Proton Stripping Generates Inside-Out Structures: A Molecular Dynamics Simulation Study
- Source :
- Chemistry Publications
- Publication Year :
- 2020
-
Abstract
- The properties of electrosprayed protein ions continue to be enigmatic, owing to the absence of high-resolution structure determination methods in the gas phase. There is considerable evidence that under properly optimized conditions these ions preserve solution-like conformations and interactions. However, it is unlikely that these solution-like conformers represent the "intrinsic" structural preferences of gaseous proteins. In an effort to uncover what such intrinsically preferred conformers might look like, we performed molecular dynamics (MD) simulations of gaseous ubiquitin. Our work was inspired by recent gas phase experiments, where highly extended 13+ ubiquitin ions were transformed to compact 3+ species by proton stripping (Laszlo, K. J.; Munger, E. B.; Bush, M. F. J. Am. Chem. Soc. 2016, 138, 9581-9588). Our simulations covered several microseconds and used a mobile-proton algorithm to account for the fact that a H+ in gaseous proteins can migrate between different titratable sites. Proton stripping caused folding of ubiquitin into heterogeneous "inside-out" structures. The hydrophilic core of these conformers was stabilized by charge-charge and polar interactions, while hydrophobic residues were located on the protein surface. Collision cross sections of these MD structures were in good agreement with experimental results. The inside-out structures generated during gas phase folding are in striking contrast to the solution behavior which is dominated by the hydrophobic effect, i.e., the tendency to bury hydrophobic side chains in the core (instead of exposing them to the surface). We do not dispute that native-like proteins can be transferred into the gas phase as kinetically trapped species. However, those metastable conformers do not represent the intrinsic structural preferences of gaseous proteins. Our work for the first time provides detailed insights into the properties of intrinsically preferred gas phase conformers, and we unequivocally find them to have inside-out architectures.
- Subjects :
- Ions
Protein Folding
Materials science
010304 chemical physics
Stripping (chemistry)
Proton
Protein Conformation
Molecular Dynamics Simulation
010402 general chemistry
01 natural sciences
0104 chemical sciences
Surfaces, Coatings and Films
Gas phase
Ion
Molecular dynamics
Chemistry
Chemical physics
0103 physical sciences
Materials Chemistry
Determination methods
Protein folding
Gases
Physical and Theoretical Chemistry
Protons
Subjects
Details
- ISSN :
- 15205207
- Volume :
- 124
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- The journal of physical chemistry. B
- Accession number :
- edsair.doi.dedup.....3ef32fa3b308d042ee77f75d8f72b395