Dynamics hydrated proteins

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. 

We recently developed a systematic method that uses the intrinsic tryptophan residue (Trp or W) as a local optical probe [49, 50]. Using site-directed mutagenesis, tryptophan can be mutated into different positions one at a time to scan protein surfaces. With femtosecond temporal and single-residue spatial resolution, the fluorescence Stokes shift of the local excited Trp can be followed in real time, and thus, the location, dynamics, and functional roles of protein-water interactions can be studied directly. With MD simulations, the solvation by water and protein (residues) is differentiated carefully to determine the hydration dynamics. Here, we focus our own work and review our recent systematic studies on hydration dynamics and protein-water fluctuations in a series of biological systems using the powerful intrinsic tryptophan as a local optical probe, and thus reveal the dynamic role of hydrating water molecules around proteins, which is a longstanding unresolved problem and a topic central to protein science. 

Because of the ease with which molecular mechanics calculations may be obtained, there was early recognition that inclusion of solvation effects, particularly for biological molecules associated with water, was essential to describe experimentally observed structures and phenomena [32]. The solvent, usually an aqueous phase, has a fundamental influence on the structure, thermodynamics, and dynamics of proteins at both a global and local level [3/]. Inclusion of solvent effects in a simulation of bovine pancreatic trypsin inhibitor produced a time-averaged structure much more like that observed in high-resolution X-ray studies with smaller atomic amplitudes of vibration and a fewer number of incorrect hydrogen bonds [33], High-resolution proton NMR studies of protein hydration in aqueous... 

Temperature and hydration level are linked in determining the dynamics of protein and solvent. The dry protein shows, for all temperatures, only the restricted motion found below the critical temperature for hydrated samples. A fully hydrated sample shows strong temperature dependence for the dynamic properties of both protein and hydration water, for temperatures above the critical temperature. Partially hydrated samples behave complexly. Goldanskii and Krupyanskii (1989) gave a particularly good discussion of the linkage between the effects of temperature and hydration. 

Kamal JKA, Zhao L, Zewail AH. Ultrafast hydration dynamics in protein unfolding Human serum albumin. Proc. Natl. Acad. Sci. U.S.A. 2004 101 13411-13416. 

To characterise the functionally Important motions in hydrated myoglobin, simulations on its hydrated CO complex have been performed by Steinbach and Brooks [35], In this study the temperature and hydration dependence of equilibrium dynamics was investigated. The authors performed two sets of MD simulations, torsionally restrained and unrestrained calculations on dehydrated carbonmonoxy myoglobin at different temperatures between 100 K and 400 K were compared to that on the hydrated protein. They found that the dehydrated protein exhibits almost exclusively harmonic fluctuations at all temperatures, while remarkable anharmonic motions have been detected in the hydrated protein at about 200 K independently whether the torsions were constrained. The... 

Zanotti, J.-M., Bellissent-Funel, M.-C., and Parello, J. (1999) Hydration-coupled dynamics in proteins studied by neutron scattering and NMR. The case of the typical EF-hand calcium-binding parvalbumin,... 

M. Tarek D.J. Tobias (2002). Phys. Rev. Lett., 89, art no. 275501. Single particle and collective dynamics of protein hydration water A molecular djmamics study. A.R. Bizzarri S. Cannistrato (2002). J. Phys. Chem. B, 106, 6617-6633. Molecular dynamics of water at the protein solvent interface. 

The aim of the present investigation is to study water dynamics in hydrated proteins while testing the cross relaxation model. According to equation 5, the temperature dependence of the observed water relaxation components could arise from changes in any of the three fundamental rate constants Riy, Rip. and Rf. Thus, extraction of R] from the observed R f and Rig in order to find its temperature dependence is necessary before a detailed interpretation in terms of water motion is attempted. 

The protein folding problem - the ability to predict a protein fold from its sequence - is one of the major prizes in computational chemistry. Molecular dynamics simulations of solvated proteins is currently not a feasible approach to this problem. However, Duan and Kollman have shown that a 1 ps simulation on a small hydrated protein, here the 36 residue villin headpiece, is now possible using a massively parallel super computer.33 The native protein is estimated to fold in about 10-100 ps and so the simulation can only be used to study the early stages of protein folding. Nevertheless, starting from an extended structure the authors were able to observe hydrophobic collapse and secondary structure formation (helix 2 was well formed, helices 1 and 3 were partially formed and the loop connecting helices 1 and 2 was also partially... 

Diakova G, Goddard YA, Korb JP, Bryant RG (2010) Water and backbone dynamics in a hydrated protein. Biophys J 98 138-146... 

We have recently used MD simulations to explore the differences in the structure, energetics, and dynamics of protein hydration water in N and MG states of HaLA. The MG state was modeled as an ensanble of 15 conformers prepared as summarized above in Section 16.2 and described in detail in Ref [5]. The root-mean squared deviation (RMSD) of the backbone heavy atom positions from the initial crystal structure ranged from 2.8 to 7.6 A, which is significantly greater than the 1.1 A RMSD of the N state simnlation. Radii of gyration demonstrated the loss of compaction of the MG conformers (R = 15.2-17.8 A) compared to the N state (R. = 14.3 A). The increase in size is accompanied by a modest increase in the... 

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