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

TL;DR

This study investigates water dynamics around hemoglobin and melittin, revealing how local hydrophobicity changes relate to protein conformational states and providing insights into the molecular mechanisms of hemoglobin's T to R transition.

Contribution

It introduces a dynamical view of water interactions with proteins, linking local hydrophobicity changes to structural transitions in hemoglobin and melittin.

Findings

LH changes correlate with T to R transition in Hb.

Water density and orientation affect Hb interface stability.

Protein flexibility influences hydration dynamics in melittin.

Abstract

The water dynamics, as characterized by the local hydrophobicity (LH), is investigated for tetrameric hemoglobin 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 alpha1 / beta2 and alpha2 / beta1 interface is accompanied by changes in LH. For Hb in cubic water boxes with 90 Aengstroem and 120 Aengstroem 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 alpha / beta 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 % than for the rigid dimer, reflecting the fact that protein and water dynamics are coupled.