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

Abstract

The water dynamics, as characterized by the local hydrophobicity (LH), is investigated for tetrameric hemoglobin (Hb) and dimeric melittin. For the T 0 to R 0 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 α 1 /β 2 and α 2 /β 1 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.

On the importance of statistics in molecular simulations for thermodynamics, kinetics and simulation box size

“…7). It is our hope that this work will provide a reference for the scientific community to identify cases that do not meet scientific standards (33).…”

“…Upon generation of a larger data sample, the previous conclusions of El Hage et al are shown not to hold ( Figure 7 ). It is our hope that this work will provide a reference for the scientific community to identify cases that do not meet scientific standards ( Pezzella et al, 2020 ).…”

Uncertainty quantification in classical molecular dynamics

“…Indeed, the ensuing debate [51][52][53][54] highlights the importance of setting up systems correctly for simulation and, more importantly, applying ensemble approaches to get statistically significant results. The issue at stake is also important for the evaluation of the reliability of scientific research, as is clear from the follow up studies by the debaters [45,55]. As we noted above, without first handling the stochastic errors, it is not possible to assess correctly the nature and magnitude of the systematic errors, and to interpret findings convincingly.…”

Using molecular dynamics simulation to study the polarization response of the liquid water interface to surface charge heterogeneity

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