Solvent Dynamics and Structure

For an understanding of protein-solvent interactions it is necessary to explore the modifications of the dynamics and structure of the surrounding water induced by the presence of the biopolymer. The theoretical methods best suited for this purpose are conventional molecular dynamics with periodic boundary conditions and stochastic boundary molecular dynamics techniques, both of which treat the solvent explicitly (Chapt. IV.B and C). We focus on the results of simulations concerned with the dynamics and structure of water in the vicinity of a protein both on a global level (i.e., averages over all solvation sites) and on a local level (i.e., the solvent dynamics and structure in the neighborhood of specific protein atoms). The methods of analysis are analogous to those commonly employed in the determination of the structure and dynamics of water around small solute molecules.163 In particular, we make use of the conditional protein solute -water radial distribution function, 

The dynamics of the solvent in the region near a protein can be characterized by a number of properties (e.g., solvent velocity correlation functions, mean-square displacement correlation functions, dipole orientation correlation functions, etc.). These properties provide information on a range of phenomena from local solute-solvent interactions (velocity correlation functions) to solvent mobility (mean-square displacement correlation functions) and dielectric behavior (dipole correlation functions). Here we focus on the diffusion constant, which provides a convenient measure of mobility for water molecules near protein atoms. The diffusion constant for solvent molecules may be computed directly from the slope of the mean-square displacement correlation function, 

Trypsin in aqueous solution has been studied by a simulation with the conventional periodic boundary molecular dynamics method and an NVT ensemble.312 340 A total of 4785 water molecules were included to obtain a solvation shell four to five water molecules thick in the periodic box the analysis period was 20 ps after an equilibration period of 20 ps at 285 K. The diffusion coefficient for the water, averaged over all molecules, was 3.8 X 10-5 cm2/s. This value is essentially the same as that for pure water simulated with the same SPC model,341 3.6 X 10-5 cm2/s at 300 K. However, the solvent mobility was found to be strongly dependent on the distance from the protein. This is illustrated in Fig. 47, where the mean diffusion coefficient is plotted versus the distance of water molecules from the closest protein atom in the starting configuration the diffusion coefficient at the protein surface is less than half that of the bulk result. The earlier simulations of BPTI in a van der Waals solvent showed similar, though less dramatic behavior 193 i.e., the solvent molecules in the first and second solvation layers had diffusion coefficients equal to 74% and 90% of the bulk value. A corresponding reduction in solvent mobility is observed for water surrounding small biopolymers.163 Thus it 

For the charged atoms (Fig. 50), all of the distribution functions show features typical of charged-group solvation.112,113 There are four to five solvent molecules within the first solvation sphere, defined as extending to the first minimum ing(r) that is at - 3.5 A. This is indicative of tightly bound solvent around the charged group. 

Results for the dynamics of water around protein sidechains in lysozyme 

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We have already emphasized the important role of the solvent dynamics and structure in the kinetics of electron-transfer reactions. During the last few years, a number of classical molecular dynamic (MD) simulations have been performed to obtain free energy surfaces of the reaction [21-27]. These simulations require explicit interaction potentials between the constituents of the system the reactants, the solvent, and the electrode. Again, a generalized solvent coordinate is used to... 

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... 

These early MD studies were limited to hard sphere or Lennard-Jones interactions appropriate for simple fluids. In the early 1970s the first attempts to apply MD methods to molecular fluids were made. Harp and Berne [11] studied a model for carbon monoxide while Rahman and Stiflinger [12] carried out MD simulations of hquid water. The MD simulations of water were especially important because they addressed questions related to the dynamics and structure of an ubiquitous solvent that would figure prominently in later work on biological and condensed phase systems. Furthermore, because of the nature of the long-range Coulomb forces in this system and the dehcate nature... 

While molecular dynamics (MD) simulations have proven to be very powerful for studying numerous aspects of protein dynamics and structure [11-13], this technique cannot yet access the millisecond-to-second time-scales required for folding even a small protein. To address this timescale gap, one has to simplify the protein model by reducing the number of degrees of freedom. Such approaches assume that the basic physics could be reproduced in model systems that employ united atoms and effective solvent models. On the basis of recent work, it has become apparent that the crux of the solution to the protein folding problem does not lie in whether a reduced protein model is used, but rather in the development of... 

Xu, Z., Lazim, R., Sun, T, Mei, Y, and Zhang, D. (2012). Solvent effect on the folding dynamics and structure of e6-associated protein characterized from ab initio protein folding simulations. The Joumai of Chemicai Physics 136,13, p. 135102. 

Kameda et al. have investigated effects of supercooling and organic solvent on the formation of a silk sponge with porous three-dimensional structure and have characterised its dynamics and structure using solid-state NMR techniques. 

We have seen that hydration forces act between lipid bilayers in aqueous and non-aqueous solvents. The molecular nature of the interaetion is beginning to be understood, and involves solvation effects along with dynamic, and structural properties of the lipid bilayer. The relative importanee of these factors is still a controversial topic. However, because of the complexity of membrane systems, one cannot expect a force, which can be described by a simple mathematical for-... 

Given a solute in equilibrium with solvent molecules, a sudden change in the solute s electronic structure due to an absorption of electromagnetic radiation or an electron transfer will generally create a nonequilibrium state. The solvent electronic and nuclear degrees of freedom will respond to reestablish equilibrium. These solvent dynamics can be monitored experimentally. Assuming an instantaneous response of the solvent electronic degrees of freedom, the slower solvent response involves translation, rotation, and vibration of the solvent molecules, which can be followed by classical molecular dynamics. Because experimental and theoretical studies of solvation dynamics can reveal important phenomena needed to understand solvent dynamics and solute-solvent interactions, they have been reviewed extensively. Solvation... 

Protein-DNA complexes present demanding challenges to computational biophysics The delicate balance of forces within and between the protein, DNA, and solvent has to be faithfully reproduced by the force field, and the systems are generally very large owing to the use of explicit solvation, which so far seems to be necessary for detailed simulations. Simulations of such systems, however, are feasible on a nanosecond time scale and yield structural, dynamic, and thermodynamic results that agree well with available experimen-... 

The structure of these globular aggregates is characterized by a micellar core formed by the hydrophilic heads of the surfactant molecules and a surrounding hydrophobic layer constituted by their opportunely arranged alkyl chains whereas their dynamics are characterized by conformational motions of heads and alkyl chains, frequent exchange of surfactant monomers between bulk solvent and micelle, and structural collapse of the aggregate leading to its dissolution, and vice versa [2-7]. 

In this section, we switch gears slightly to address another contemporary topic, solvation dynamics coupled into the ESPT reaction. One relevant, important issue of current interest is the ESPT coupled excited-state charge transfer (ESCT) reaction. Seminal theoretical approaches applied by Hynes and coworkers revealed the key features, with descriptions of dynamics and electronic structures of non-adiabatic [119, 120] and adiabatic [121-123] proton transfer reactions. The most recent theoretical advancement has incorporated both solvent reorganization and proton tunneling and made the framework similar to electron transfer reaction, [119-126] such that the proton transfer rate kpt can be categorized into two regimes (a) For nonadiabatic limit [120] ... 

The importance of water molecules for the structural dynamics and the functioning of ribozymes was investigated by Rhodes and co-workers. They studied non-coded RNA using a combination of explicit solvent molecular dynamics and single molecule fluorescence spectroscopy approaches (Rhodes et al 2006). 

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