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The unique features of a macromolecule and water as a solvent make the issue of solvation unconventional, with questions about the static versus dynamic nature of hydration and the physics of orientational and translational diffusion at the boundary. For proteins, the hydration shell that covers the surface is critical to the stability of its structure and function. Dynamically speaking, the residence time of water at the surface is a signature of its mobility and binding. With femtosecond time resolution it is possible to unravel the shortest residence times which are key for the description of the hydration layer, static or dynamic. In this article we review these issues guided by experimental studies, from this laboratory, of polar hydration dynamics at the surfaces of two proteins (Subtilisin Carlsberg (SC) and Monellin). The natural probe tryptophan amino acid was used for the interrogation of the dynamics, and for direct comparison we also studied the behavior in bulk watersa complete hydration in 1 ps. We develop a theoretical description of solvation and relate the theory to the experimental observations. In this theoretical approach, we consider the dynamical equilibrium in the hydration shell, defining the rate processes for breaking and making the transient hydrogen bonds, and the effective friction in the layer which is defined by the translational and orientational motions of water molecules. The relationship between the residence time of water molecules and the observed slow component in solvation dynamics is a direct one. For the two proteins studied, we observed a "bimodal decay" for the hydration correlation function, with two primary relaxation times: ultrafast, typically 1 ps or less, and longer, typically 15-40 ps, and both are related to the residence time at the protein surface, depending on the binding energies. We end by making extensions to studies of the denatured state of the protein, random coils, and the biomimetic micelles, and conclude with our thoughts on the relevance of the dynamics of native structures to their functions.

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The optical, electronic and mechanical properties of synthetic and biological materials consisting of polymer chains depend sensitively on the conformation adopted by these chains. The range of conformations available to such systems has accordingly been of intense fundamental as well as practical interest, and distinct conformational classes have been predicted, depending on the stiffness of the polymer chains and the strength of attractive interactions between segments within a chain. For example, flexible polymers should adopt highly disordered conformations resembling either a random coil or, in the presence of strong intrachain attractions, a so-called 'molten globule'. Stiff polymers with strong intrachain interactions, in contrast, are expected to collapse into conformations with long-range order, in the shape of toroids or rod-like structures. Here we use computer simulations to show that the anisotropy distribution obtained from polarization spectroscopy measurements on individual poly[2-methoxy-5-(2'-ethylhexyl)oxy-1,4-phenylenevinylene] polymer molecules is consistent with this prototypical stiff conjugated polymer adopting a highly ordered, collapsed conformation that cannot be correlated with ideal toroid or rod structures. We find that the presence of so-called 'tetrahedral chemical defects', where conjugated carbon-carbon links are replaced by tetrahedral links, divides the polymer chain into structurally identifiable quasi-straight segments that allow the molecule to adopt cylindrical conformations. Indeed, highly ordered, cylindrical conformations may be a critical factor in dictating the extraordinary photophysical properties of conjugated polymers, including highly efficient intramolecular energy transfer and significant local optical anisotropy in thin films.

Dielectric relaxation and NMR spectrum of water in biological systems such as proteins, DNA, and reverse micelles can often be described by two widely different time constants, one of which is in the picosecond while the other is in the nanosecond regime. Although it is widely believed that the bimodal relaxation arises from water at the hydration shell, a quantitative understanding of this important phenomenon is lacking. In this article we present a theory of dielectric relaxation of biological water. The time dependent relaxation of biological water is described in terms of a dynamic equilibrium between the free and bound water molecules. It is assumed that only the free water molecules undergo orientational motion; the bound water contribution enters only through the rotation of the biomolecule, which is also considered. The dielectric relaxation is then determined by the equilibrium constant between the two species and the rate of conversion from bound to free state and vice versa. However, the dielectric relaxation in such complex biomolecular systems depends on several parameters such as the rotational time constant of the protein molecule, the dimension of the hydration shell, the strength of the hydrogen bond, the static dielectric constant of the water bound to the biomolecule, etc. The present theory includes all these aspects in a consistent way. The results are shown to be in very good agreement with all the known results. The present study can be helpful in understanding the solvation of biomolecules such as proteins.

Although water is often hailed as the lubricant of life, a detailed understanding of its role in many chemical and biological processes still eludes us. In many natural systems, water is confined in an environment where its free movement is restricted and its three-dimensional hydrogen-bonded network is disrupted. Very recently, several groups applied ultrafast laser spectroscopy to study the dynamics of the constrained water molecules. It is observed that the dynamic behavior of the confined water molecules is markedly different from that of the ordinary water molecules. The most striking result is the bimodal response of confined water, with one bulk water-like subpicosecond component and a much slower component in a time scale of hundreds or thousands of picoseconds. This slow second component constitutes 10−30% of the total response and is crucial in the understanding of the role of water in complex chemical and biological processes. The origin of the slow component has been a subject of intense recent debate and has recently been attributed to a dynamic exchange between free and bound water. This interpretation seems to be in accord with the conclusion reached independently by intermolecular solute−water NOE and NMRD studies. In this article, a review of the recent experimental and theoretical work in this area is presented.

It is known that DNA-binding proteins can slide along the DNA helix while searching for specific binding sites, but their path of motion remains obscure. Do these proteins undergo simple onedimensional (1D) translational diffusion, or do they rotate to maintain a specific orientation with respect to the DNA helix? We measured 1D diffusion constants as a function of protein size while maintaining the DNA-protein interface. Using bootstrap analysis of single-molecule diffusion data, we compared the results to theoretical predictions for pure translational motion and rotation-coupled sliding along the DNA. The data indicate that DNA-binding proteins undergo rotation-coupled sliding along the DNA helix and can be described by a model of diffusion along the DNA helix on a rugged free-energy landscape. A similar analysis including the 1 D diffusion constants of eight proteins of varying size shows that rotation-coupled sliding is a general phenomenon. The average free-energy barrier for sliding along the DNA was 1.1 ± 0.2 k B T. Such small barriers facilitate rapid search for binding sites.Many nucleic acid enzymes and proteins that act on DNA quickly locate target sites by diffusing along nonspecific DNA. It has been shown that proteins can both hop and slide along doublestranded DNA [1][2][3] , although the microscopic mechanism of protein motion along DNA molecules is still not understood in molecular detail. In particular, the path traced by a sliding protein molecule along the surface of DNA has not been established. Both linear paths, parallel to the DNA axis, and helical paths, following a strand or groove of the DNA around the DNA axis, have been taken as assumptions in biophysical and biochemical models. Although rotation of sliding proteins around the DNA helix was implicitly 4 and explicitly 5,6 anticipated, such rotation was not shown to occur during diffusive sliding. The concept of rotational coupling has also arisen among structural biologists based on concepts of molecular recognition and observations of detailed structural complementarity between proteins and DNA 7-9 . Despite © 2009 Nature America, Inc. All rights reserved.Correspondence to: Biman Bagchi; X Sunney Xie.Correspondence should be addressed to B.B. (bagchibiman@yahoo.com) the persistent high profile of this question in the literature, it remains unknown whether sliding proteins track the DNA helix. Such tracking would have major biophysical and biochemical implications: for example, only a limited set of enzyme-helix juxtapositions would need to be considered in questions of protein-DNA interaction. In this work, we examine the dependence on protein size of the diffusion constant for sliding along DNA in order to distinguish pure translational diffusion (Fig. 1a) along DNA from rotation-coupled (or -slaved) diffusion (Fig. 1b). The result offers insights into the mechanism of target search and recognition of all DNAbinding proteins.As a protein moves along DNA, it experiences three different frictional forces arising from rando...

The dynamics of hydrogen bonds among water molecules themselves and with the polar head groups (PHG) at a micellar surface have been investigated by long molecular dynamics simulations. The lifetime of the hydrogen bond between a PHG and a water molecule is found to be much longer than that between any two water molecules, and is likely to be a general feature of hydrophilic surfaces of organized assemblies. Analyses of individual water trajectories suggest that water molecules can remain bound to the micellar surface for more than 100 ps. The activation energy for such a transition from the bound to a free state for the water molecules is estimated to be about 3.5 kcal/mol.