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The static and frequency-dependent dielectric properties of a 9 mmol/L ubiquitin solution based on the analysis of a 5 ns molecular dynamics (MD) simulation is reported. It is demonstrated that an MD-based approach can qualitatively reproduce measured dielectric properties of protein solutions and aid in the interpretation of the experimental data. The findings reveal that protein and water self-contributions could be obtained with reasonable accuracy, while some problems were detected for the protein-water cross-term.

We report molecular dynamics simulations of three globular proteins: ubiquitin, apo-calbindin D9K, and the C-terminal SH2 domain of phospholipase C-γ1 in explicit water. The proteins differ in their overall charge and fold type and were chosen to represent to some degree the structural variability found in medium-sized proteins. The length of each simulation was at least 15 ns, and larger than usual solvent boxes were used. We computed radial distribution functions, as well as orientational correlation functions about the surface residues. Two solvent shells could be clearly discerned about charged and polar amino acids. Near apolar amino acids the water density near such residues was almost devoid of structure. The mean residence time of water molecules was determined for water shells about the full protein, as well as for water layers about individual amino acids. In the dynamic properties, two solvent shells could be characterized as well. However, by comparison to simulations of pure water it could be shown that the influence of the protein reaches beyond 6 Å, i.e., beyond the first two shells. In the first shell (r≤=3.5 Å), the structural and dynamical properties of solvent waters varied considerably and depended primarily on the physicochemical properties of the closest amino acid side chain, with which the waters interact. By contrast, the solvent properties seem not to depend on the specifics of the protein studied (such as the net charge) or on the secondary structure element in which an amino acid is located. While differing considerably from the neat liquid, the properties of waters in the second solvation shell (3.5≤r≤=6 Å) are rather uniform; a direct influence from surface amino acids are already mostly shielded. [ABSTRACT FROM AUTHOR]

We report molecular dynamics (MD) simulations of three protein-water systems (ubiquitin, apo-calbindin D9K, and the C-terminal SH2 domain of phospholipase C-γ1), from which we compute the dielectric properties of the solutions. Since two of the proteins studied have a net charge, we develop the necessary theory to account for the presence of charged species in a form suitable for computer simulations. In order to ensure convergence of the time correlation functions needed for the analysis, the minimum length of the MD simulations was 20 ns. The system sizes (box length, number of waters) were chosen so that the resulting protein concentrations are comparable to experimental conditions. A dielectric component analysis was carried out to analyze the contributions from protein and water to the frequency-dependent dielectric susceptibility χ(ω) of the solutions. Additionally, an even finer decomposition into protein, two solvation shells, and the remaining water (bulk water) was carried out. The results of these dielectric decompositions were used to study protein solvation at mesoscopic resolution, i.e., in terms of protein, first and second solvation layers, and bulk water. This study, therefore, complements the structural and dynamical analyses at molecular resolution that are presented in the companion paper. The dielectric component contributions from the second shell and bulk water are very similar in all three systems. We find that the proteins influence the dielectric properties of water even beyond the second solvation shell, in agreement with what was observed for the mean residence times of water molecules in protein solutions. By contrast, the protein contributions, as well as the contributions of the first solvation shell, are system specific. Most importantly, the protein and the first water shell around ubiquitin and apo-calbindin are anticorrelated, whereas the first water shell around the SH2 domain is positively correlated. [ABSTRACT FROM AUTHOR]

An intermolecular potential for liquid hydrogen chloride is derived from ab initio calculations and is further refined by using solid state properties. The potential function includes a two-center Lennard-Jones term, a six-center point charge model and many-body polarization forces. Monte Carlo calculations are performed for two densities (ρ=0.85 g/cm3, 0.50 g/cm3) at two temperatures (T=25 °C, 100 °C). The relative importance of the various contributions to the intermolecular potential are elucidated by comparison to neutron diffraction experiments. [ABSTRACT FROM AUTHOR]

The shortcomings present in the Nandi and Bagchi's (NB's) approach to explain the dielectric relaxation spectra of an aqueous protein solution via the first unified, microscopic theory is discussed. It is stated that the alleged rationalization of dielectric spectra of protein solutions provided by NB relies on a wrong starting equation combined with an incorrect definition of the Kirkwood g-factor.

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983. © 2009 Wiley Periodicals, Inc.J Comput Chem, 2009. [ABSTRACT FROM AUTHOR]

We report molecular dynamics (MD) simulations of aqueous solutions of glucose and maltose. For each sugar, two concentrations were studied. The static and frequency-dependent dielectric properties of the solutions were calculated from MD trajectories of at least 5 ns length and compared to those of pure water. The contributions from the solute, the solvent, and the solute-solvent cross term were analyzed. In addition, for the more dilute glucose and maltose solutions a Voronoi analysis was carried out to distinguish between contributions from the first water shell and from unbound bulk water. The results of the glucose simulations were compared to available experimental data. While the static dielectric constant of the four solutions was found to be very similar to that of pure water, a number of differences could be discerned in the dielectric spectra. These findings for the overall frequency-dependent dielectric susceptibilities were rationalized by a dielectric component analysis. The importance of contributions from cross terms and from the solute depended on solute type (glucose or maltose) and concentration. In particular, we observed a linear correlation between the contribution of the solute-solvent cross term and the total number of hydroxyl groups of the solute (i.e., the number of solute molecules times the number of hydroxyl groups in a glucose or maltose molecule, respectively). The dielectric properties of water in the solutions could be rationalized as the superposition of two contributions, one originating from the bulklike free waters, the other from the waters in the first hydration shell of the saccharides. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]