Water dynamics around T vs R4 of hemoglobin from local hydrophobicity analysis
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025101_1_online.pdf
Description
Published version
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6.43 MB
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Author(s)
Salehi, Seyedeh Maryam
Pezzella, Marco
Willard, Adam
Meuwly, Markus
Karplus, Martin
Date Issued
January 10, 2023
Journal
The Journal of Chemical Physics
Publisher
AIP Publishing
Citation
Seyedeh Maryam Salehi, Marco Pezzella, Adam Willard, Markus Meuwly, Martin Karplus; Water dynamics around T vs R4 of hemoglobin from local hydrophobicity analysis. J. Chem. Phys. 14 January 2023; 158 (2): 025101.
Version
Final published version
Abstract
The local hydration around tetrameric hemoglobin (Hb) in its T0 and R4 conformational substates is analyzed based on molecular dynamics simulations. Analysis of the local hydrophobicity (LH) for all residues at the α1β2 and α2β1 interfaces, responsible for the quaternary T → R transition, which is encoded in the Monod–Wyman–Changeux model, as well as comparison with earlier computations of the solvent accessible surface area, makes clear that the two quantities measure different aspects of hydration. Local hydrophobicity quantifies the presence and structure of water molecules at the interface, whereas “buried surface” reports on the available space for solvent. For simulations with Hb frozen in its T0 and R4 states, the correlation coefficient between LH and buried surface is 0.36 and 0.44, respectively, but it increases considerably if the 95% confidence interval is used. The LH with Hb frozen and flexible changes little for most residues at the interfaces but is significantly altered for a few select ones: Thr41α, Tyr42α, Tyr140α, Trp37β, Glu101β (for T0) and Thr38α, Tyr42α, Tyr140α (for R4). The number of water molecules at the interface is found to increase by ∼25% for T0 → R4, which is consistent with earlier measurements. Since hydration is found to be essential to protein function, it is clear that hydration also plays an essential role in allostery.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1063/5.0129990
