Lysozyme water dynamics

Keywords Structure Dynamics Intermolecular interaction Lysozyme Water Diffusion... 

A detailed examination of LN behavior is available [88] for the blocked alanine model, the proteins BPTI and lysozyme, and a large water system, compared to reference Langevin trajectories, in terms of energetic, geometric, and dynamic behavior. The middle timestep in LN can be considered an adjustable quantity (when force splitting is used), whose value does not significantly affect performance but does affect accuracy with respect to the reference trajectories. For example, we have used Atm = 3 fs for the proteins in vacuum, but 1 fs for the water system, where librational motions are rapid. 

To provide an understanding of the importance of solvent mobility and the intrinsic protein energy surface, an MDS of proteins and surrounding solvent molecules at different temperatures has been performed. The simulation of myoglobin dynamics showed that solvent mobility is the dominant factor in determining protein atomic fluctuations above 180 K (Vitkup et ah, 2000). The drastic effects of water molecule dynamics on the intramolecular motion of RNase and xylase was demonstrated in recent computer simulation studies (Reat et al., 2000 Tarek et al, 2000). Extensive simulations were carried out to identify the time-scale of water attachment to lysozyme (Steprone et... 

As an example, we will consider the molecular dynamical behavior of egg white lysozyme. The temperature dependence of mobility of fluorescence, spin and Mossbauer labels attached to lysozyme was found to be similar to other investigated proteins the monotonic increase typical for rigid polymers in dry states and in samples with water content (wt) was less than the critical value (wtcr) and drastically burst when wt > wtcr at T > 200 K took place (Frolov et al., 1978 Likhtenshtein, 1979). At similar conditions, experiments on the temperature dependence of heat capacity indicated only a monotonic steady increase for rigid organic material. Recently, in the fully dried lysozyme crystal, similar monotonic behavior of heat capacity was observed in temperatures between 8 and 30°C. At D20 content more than 24 wt %, a slight deviation from the monotony was observed at temperatures above approximately 185 K, which most probably is due to the eutectic melting of NaCl/2H20 present in the samples to prevent water crystallization (Miyazaki et al., 2000). 

Tsai, A.M., Neumann, D.A., and Bell, L.N. (2000) Molecular dynamics of solid-state lysozyme as affected by glycerol and water a neutron scattering study, Biophys. J. 79, 2728-2732. 

Proteins in the dry state are frozen. They only open up and start moving if some water is added, as in nature. It turns out that protein movements in, e.g., lysozyme are activated only when there is 0.15 g of water per gram of protein, a good example of the effect of hydration on living processes. However, it is difficult to examine protein dynamics in solution because to make a satisfactory interpretation of the observations, one would have first to do the corresponding spectroscopy in the dry state this is difficult because of the frozen state referred to and a tendency to decompose. 

This section discusses a selection of NMR results with an emphasis on powder studies, on experiments that describe the dynamics of water at the protein surface, and on lysozyme as a model protein. Methods and theory are not discussed. For review discussions see Kuntz and Kauz-mann (1974), Bryant (1978), Koenig (1980), and Fung (1986). A recent review by Bryant (1988) is an elegant summary of the theory and results for NMR measurements of protein hydration, in powders and in solution. 

In an investigation of the role of water in enzymic catalysis. Brooks and Karplus (1989) chose lysozyme for their study. Stochastic boundary molecular dynamics methodology was applied, with which it was possible to focus on a small part of the overall system (i.e., the active site, substrate, and surrounding solvent). It was shown that both structure and dynamics are affected by solvent. These effects are mediated through solvation of polar residues, as well as stabilization of like-charged ion pairs. Conversely, the effects of the protein on solvent dynamics and... 

Kossiakoff (1985) pointed out that the most useful attribute of neutron diffraction studies of proteins (compared with X-ray diffraction) is their ability to locate hydrogen (or deuterium) experimentally. Recent advances in apparatus and data acquisition mean that this method will become increasingly valuable in the study of a-lactalbumin and lysozyme, especially in the location of water molecules and the dynamics of these proteins. An example of a recent application is that by Lehmann et al. (1985). 

The formation of spanning H-bonded water networks on the surface of biomolecules has been connected with the widely accepted view that a certain amount of hydration water is necessary for the dynamics and function of proteins. Its percolative nature had been suggested first by Careri et al. (59) on the basis of proton conductivity measurements on lysozyme this hypothesis was later supported by extensive computer simulations on the hydration of proteins like lysozyme and SNase, elastine like peptides, and DNA fragments (53). The extremely interesting... 

These CMD results are still qualitative and somewhat conflicting with the available experimental data [55], largely because of the simplified models used for the surfaces and more certainly due to difficulties in choosing suitable potential functions for the simulations. However, recently, molecular dynamic simulations of the hen egg-white lysozyme-Fab D1.3 complex have been reported both the crystal state and the complex in solution were studied [35]. The findings are consistent with the observation by various experimentalists of a reduced water mobility in a region extending several angstroms beyond the first hydration layer [54-57], as reported also from CMD simulations [60]. 

J. Xu, K. W. Plaxco and S. J. Allen, Collective dynamics of lysozyme in water terahertz absorption spectroscopy and comparison with theory, submitted. 

The basic partitioning is illustrated schematically in Fig. 8a and realistically in Fig. 8b for a simulation study focusing on the dynamics of a tryptophan ring in the protein lysozyme.108 With the division indicated in the figure the total number of atoms to be simulated is 696 (294 protein atoms and 134 water molecules). This is a great reduction from the estimated 11,766 atoms (1266 protein atoms and 3500 water molecules) that would be necessary if conventional periodic boundary conditions were employed the estimate is based on using a 50-A cubic cell, a 26-A sphere to represent lysozyme, and 1 g/cm3 density for water. 

Results for the dynamics of water around protein sidechains in lysozyme... 

In the active-site simulations of lysozyme108 (this chapter, Sect. B.2 above) similar water networks that stabilize charged groups have been observed. To illustrate the dynamics of the formation of such networks, a sequence of stereo plots showing the formation and evolution of a stable pair of positively charged residues is displayed in Fig. 56. The pair consists of (NH2)+ moieties of Arg-61 and Arg-73. The solvated structure evolved from a conformation obtained in a vacuum simulation of lysozyme.108,192 The sequence of plots shows the formation of the water-bridged pair over a time period from t = 0 ps to t 8 ps, which followed dynamical equilibration of the solvent around the fixed vacuum structure of the protein. After 8 ps, the ion-pair structure is stable, but fluctuations in the pattern of hydrogen bonds do occur typical... 

Dynamic surface tension of two protein solutions at the water/air interface 7.3-IO wt% B-casein ( ), 7.610 wt% lysozyme ( ) according to Graham Phillips (1979a)... 

A clear picture of the difference in dynamics between bulk water and biological water can be seen in Figure 6.1. Here we plot the running trajectory of the angular displacement of a randomly chosen and tagged water molecule, separately for one in bulk water and one on the surface of a protein. The tagged water molecule is at the surface of a protein lysozyme. In bulk, a water molecule undergoes frequent... 

The absence of slow dynamics in this system can be attributed to the fact that the penta-alanine peptide does not have any polar side-chain atom which can form a strong HB with water. With a higher level of hydration, the rotational dynamics of water approached that of bulk water, again as expected. A QENS study of protein dynamics was also carried out on the picosecond timescale of a protein, lysozyme solvated in glycerol at different water contents, h (g water/g lysozyme). For all h, a well-visible low-frequeney vibrational bump was observed. The quasi-elastic scattering can be decomposed into two Lorentzian components, corresponding to motions with charaeteristic time constants of 15 ps and 0.8 ps. The 15 ps component is the slow component, which is in the same range observed in many other experimental studies. 

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