Water Dynamics Around Proteins: T- and R-States of Hemoglobin and Melittin

Marco Pezzella (1) , Krystel El Hage (1, 2) , Michiel Niesen (3) , Sucheol Shin (4) , Adam Willard (3) , Markus Meuwly (1) , Martin Karplus (5)

1 Department of Chemistry [Basel]
2 SABNP - Structure et activité des biomolécules normales et pathologiques
3 Chemistry Department [Massachusetts Institute of Technology]
4 University of Texas at Austin [Austin]
5 Department of Chemistry and Chemical Biology [Harvard]

The water dynamics, as characterized by the local hydrophobicity (LH), is investigated for tetrameric hemoglobin (Hb) and dimeric melittin. For the T₀ to R₀ transition in Hb, it is found that LH provides additional molecular-level insight into the Perutz mechanism, i.e., the breaking and formation of salt bridges at the α₁/β₂ and α₂/β₁ interface is accompanied by changes in LH. For Hb in cubic water boxes with 90 and 120 Å edge length it is observed that following a decrease in LH as a consequence of reduced water density or change of water orientation at the protein/water interface the α/β interfaces are destabilized; this is a hallmark of the Perutz stereochemical model for the T to R transition in Hb. The present work thus provides a dynamical view of the classical structural model relevant to the molecular foundations of Hb function. For dimeric melittin, earlier results by Cheng and Rossky [ Nature 1998, 392, 696−699] are confirmed and interpreted on the basis of LH from simulations in which the protein structure is frozen. For the flexible melittin dimer, the changes in the local hydration can be as much as 30% greater than for the rigid dimer, reflecting the fact that protein and water dynamics are coupled.

Domains: Life Sciences [q-bio]

Marco Pezzella, Krystel El Hage, Michiel Niesen, Sucheol Shin, Adam Willard, et al.. Water Dynamics Around Proteins: T- and R-States of Hemoglobin and Melittin. Journal of Physical Chemistry B, 2020, 124 (30), pp.6540-6554. ⟨10.1021/acs.jpcb.0c04320⟩. ⟨hal-02969027⟩