Protein hydration layer

In sharp contrast to the large number of experimental and computer simulation studies reported in literature, there have been relatively few analytical or model dependent studies on the dynamics of protein hydration layer. A simple phenomenological model, proposed earlier by Nandi and Bagchi [4] explains the observed slow relaxation in the hydration layer in terms of a dynamic equilibrium between the bound and the free states of water molecules within the layer. The slow time scale is the inverse of the rate of bound to free transition. In this model, the transition between the free and bound states occurs by rotation. Recently Mukherjee and Bagchi [14] have numerically solved the space dependent reaction-diffusion model to obtain the probability distribution and the time dependent mean-square displacement (MSD). The model predicts a transition from sub-diffusive to super-diffusive translational behaviour, before it attains a diffusive nature in the long time. However, a microscopic theory of hydration layer dynamics is yet to be fully developed. 

It is now expected that moleeular motions of water in different restricted systems may show signatures of the above anomaly. This has been verified already for the protein hydration layer. But further studies are required in other systems. 

Initial information about the protein hydration layer came from relaxation studies. Dielectric relaxation (DR) and NMR studies were the first to reveal the existence of water molecules in the restricted environments. Dielectric relaxation measurements show the existence of an additional dispersion in protein solutions with time constants in the 40-50 ps time range (to be contrasted with 8 ps for bulk water), while NMR estimates have varied from system to system, with claims ranging from slow (with lifetimes in excess of 300 ps) to fast (with lifetimes 2-5 ps). The general consensus now appears to be consistent with the DR data. 

One way to understand the protein hydration layer is to go to the low-temperature limit so that the dynamics slows down and one can hopefully discern different types of motion. Such studies have been carried out, both by experiments and by simulations. Neutron-scattering experiments show a sharp change in the molecular motions of a hydrated protein around 220 K, which has been attributed to a glass transition in the protein. The change is measured in the mean-square displacements of the protein atoms. The mean-square displacement shows a rapid increase as the temperature is increased beyond 220 K (see Figure 6.3)[7]. 

Water molecules in the protein hydration layer have a finite residence time. No single water molecule stays in the layer forever, as it makes sojourn between the layer and the bulk. This residence time can play a critical role in protein association because it offers a quantitative estimate of the rigidity of the layer. The final act of association of two proteins may require partial desolvation around the necessary amino acid residue sites. This is only possible if the residence time of water around these sites is sufficiently short. The residence time is determined by the dynamics in the hydration layer. This correlation between hydration layer and protein association is an important problem that deserves careful attention. 

Dielectric relaxation can thus provide important information about the rotational time constant of proteins which in turn provides valuable information about the thickness of the protein hydration layer, as discussed below. 

The above procedure provided historically the first estimate of the width of the protein hydration layer. The estimate (3—4 A) so obtained was believed to be fairly accurate for a long time, till newer time-dependent studies and computer simulations became available. 

It is rather fascinating to note that the dynamic properties of the protein hydration layer have been studied by so many different techniques. Initially, there was controversy about the accuracy of the different techniques employed. The situation became cleared when proper care was taken to isolate and interpret the results. For example, DR and SD are mostly sensitive to the rotational motion of the water molecules and the protein side-chain motions, while NOE is sensitive to the relative translational motion between the protein and the water molecules. Naturally they... 

Understanding the protein hydration layer lessons from computer simulations... 

The above definitions are particularly suitable for investigations in computer simulations. They can be applied also to a fictitious layer in the bulk liquid, except that in the latter case decay can happen by molecules crossing across the region -that is, by penetrating the sphere not allowed in the case of protein. In the case of the protein hydration layer, these survival correlation functions decay slowly for the hydration layer. 

In the protein hydration layer water can form two types of HBs one with water itself (water-water HB, and other one with protein atoms (protein-water HB). 

Dielectric relaxation results are proven to be the most definitive to infer the distinctly different dynamic behavior of the hydration layer compared to bulk water. However, it is also important to understand the contributions that give rise to such an anomalous spectrum in the protein hydration layer, and in this context MD simulation has proven to be useful. The calculated frequency-dependent dielectric properties of an ubiquitin solution showed a significant dielectric increment for the static dielectric constant at low frequencies but a decrement at high frequencies [8]. When the overall dielectric response was decomposed into protein-protein, water-water, and water-protein cross-terms, the most important contribution was found to arise from the self-term of water. The simulations beautifully captured the bimodal shape of the dielectric response function, as often observed in experiments. 

Understanding the protein hydration layer lessons from computer simulations 9.6 Explanation of anomalous dynamics in the hydration layer... 

Free-energy barrier for escape of water molecules from protein hydration layer... 

The enormous importance of the protein hydration layer is the reason for the continued study and discussions of this topic over the last half century. It has also led to controversy and confusion, to an extent that one is reminded of the story of the... 

In the present chapter we discussed quantitative aspects of protein hydration-layer dynamics. Because of the complexity of the problem and perhaps due to a certain lack of concerted effort, there are still many issues remained to be settled. 

S. Roy and B. Bagchi, Free energy barriers for escape of water molecules from protein hydration layer. J. Phys. Chem. B, 116 (2012), 2958-2968. 

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