Protein-water interactions, role

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. 

Of great interest in both chemistry and biology is the role of water in the biological functions of proteins, DNA, and lipids, etc. This is a hard problem. In many of the early studies on protein-water interactions, water was approximated as a continuum solvent. For example, in protein rotation, one endowed the protein with a rigid boundary layer of water with the combined unit rotating in a continuum solvent. In the case of DNA, one employed concepts from electrostatics such as the double layer and employed the Poisson-Boltzmann equation. Such an approach was bound to be inadequate. Nevertheless, it was pursued for quite some time. Such a macroscopic approach fails to provide dynamic information at a molecular level. 

Protein-water interaction plays an important role in the determination and maintenance of the three-dimensional structure of proteins. Water modified the physicochemical properties of proteins. Therefore, protein-water interactions have been the subject of intensive study and have provided significant advances in our understanding of the involvement of water in protein functionality, stability, and dynamics [6]. The thermodynamics of protein-water interaction directly affects dispersibility, wettability, swelling, and solubility of proteins. Surface-active properties of proteins are simply the result of the thermodynamically unfavorable interaction of exposed nonpolar patches of proteins with solvent water. 

Although there are no positive Indications that structured water plays a role in the mechanism of muscle contraction, a theoretical mechanism employing the Ice lattice can be devised. Such a scheme uses protein-water interactions In two phases Involving Interchanging enol and keto forms of the peptide carbonyls, and was first mentioned as a possible contraction mechanism In an Informal discussion A coiq>lete elaboration of this concept as a model for muscle contraction has been publlshed. This model, which employs water In an active structural and mechanical sense, may be relevant to the earlier observation of Goodall that proton transfer could be the rate-determining step in muscle contraction. Home and Johnson have shown that variables such as pressure, ten erature, and Isotope (D2O) may Influence proton transfer In the aqueous environment, and each of these variables has been shown to have an effect on muscle contraction. 

Where this factor plays a role, the hydrophobic interaction between the hydrocarbon chains of the surfactant and the non-polar parts of protein functional groups are predominant. An example of this effect is the marked endothermic character of the interactions between the anionic CITREM and sodium caseinate at pH = 7.2 (Semenova et al., 2006), and also between sodium dodecyl sulfate (SDS) and soy protein at pH values of 7.0 and 8.2 (Nakai et al., 1980). It is important here to note that, when the character of the protein-surfactant interactions is endothermic (/.< ., involving a positive contribution from the enthalpy to the change in the overall free energy of the system), the main thermodynamic driving force is considered to be an increase in the entropy of the system due to release into bulk solution of a great number of water molecules. This entropy... 

Schwabe, J.W.R. (1997) The role of water in protein-DNA interactions. Curr. Opin. Struct. Biol. 7, 126-134. 

An examination of the important role of water in both the specificity and the affinity of protein-DNA interactions. 

MD simulations with either protein or water constrained at the instant of photoexcitation were performed for both isomer 1 and isomer 2. For isomer 1, because surface water relaxation dominates the slow component of the total Stokes shift, in Fig. 44a we show the result of simulations of isomer 1 with an ensemble of frozen protein configurations to examine the role of protein fluctuations. Clearly the long component of indole-water interactions disappears when the protein is constrained. This result shows that without protein fluctuations, indole-water relaxation over tens of picoseconds does not occur. Thus, although surface hydrating water molecules seem to drive the global solvation and, from the dynamics of the protein and water contributions, are apparently responsible for the slowest component of the solvation Stokes shift for isomer 1 (Fig. 42), local protein fluctuations are still required to facilitate this rearrangement process. When the protein is frozen, the ultrafast... 

Many hydrophobic molecules such as vitamin A, vitamin D and steroid hormones play vital roles in a variety of cellular processes. Because of the low solubility of these molecules in water, it has been difficult to measure the binding properties of the site-directed mutants of the proteins that interact with these hydrophobic ligands such as cellular retinoic acid binding proteins (CRABPs) (Zhang et al. 1992 Chen et al. 1995). This has greatly hampered the studies of the quantitative structure-function relationships of these important proteins. 

It is now well established that proteins can induce phase transitions in lipid membranes, resulting in new structures not found in pure lipid-water systems (c/. section 5.1). However, this property is not peculiar to proteins the same effect can be induced by virtually any amphiphilic molecule. Depending on the structure and nature of proteins, their interactions with lipid bilayers can be manifested in very different ways. We may further assume that the role of proteins in the biogenesis of cubic membranes is analogous to that in condensed systems, and lipids are necessary for the formation of a cubic membrane. This assumption is supported by studies of membrane oxidation, which induce a structure-less proteinaceous mass [113]. However, the existence of a lipid bilayer by itself does not guarantee the formation of a cubic membrane, as proteins may also play an essential role in setting the membrane curvature. In this context, note that the presence of chiral components e.g. proteins) may induce saddle-shaped structures characteristic of cubic membranes. (This feature of chiral packings has been discussed briefly in section 4.14)... 

The dipole potential of a lipid membrane is manifested between the hydrocarbon core of the membranes and the first few water molecules adjacent to the lipid head groups (Brockman, 1994). This potential is caused by the uniform orientation of the phosphocholine moiety, the carbonyl groups of the ester union, and, to some extent, by the presence of polarizable groups in the membrane hydrocarbon phase (Voglino et al., 1998 McIntosh, 2002). Therefore, in addition to steric hindrance and electrostatic forces, the hydration of the phospholipids plays a significant role in protein-membrane interactions as a participant in the short-range repulsive forces (McIntosh, 2002). 

Most of the electronic structure calculations have concentrated on (1) the structure, (2) long-range interaction, (3) peptide-water interaction, and (4) electronic properties. These studies have also affirmed the central role played by the H-bonding interactions in protein. The possibility of the AIM theory to analyze a polypeptide or a particular portion of a peptide has been described [6,323,324]. The existence of H-bond in the peptides has been confirmed by the presence of corresponding bond path in the electron density. Properties associated with the path have also been characterized in terms of p r ) at HBCPs and ring CPs. 

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