Data_Sheet_1_How Does Solvation Layer Mobility Affect Protein Structural Dynamics?.docx

<p>Solvation is critical for protein structural dynamics. Spectroscopic studies have indicated relationships between protein and solvent dynamics, and rates of gas binding to heme proteins in aqueous solution were previously observed to depend inversely on solution viscosity. In this work, the solvent-compatible enzyme Candida antarctica lipase B, which functions in aqueous and organic solvents, was modeled using molecular dynamics simulations. Data was obtained for the enzyme in acetonitrile, cyclohexane, n-butanol, and tert-butanol, in addition to water. Protein dynamics and solvation shell dynamics are characterized regionally: for each α-helix, β-sheet, and loop or connector region. Correlations are seen between solvent mobility and protein flexibility. So, does local viscosity explain the relationship between protein structural dynamics and solvation layer dynamics? Halle and Davidovic presented a cogent analysis of data describing the global hydrodynamics of a protein (tumbling in solution) that fits a model in which the protein's interfacial viscosity is higher than that of bulk water's, due to retarded water dynamics in the hydration layer (measured in NMR τ₂ reorientation times). Numerous experiments have shown coupling between protein and solvation layer dynamics in site-specific measurements. Our data provides spatially-resolved characterization of solvent shell dynamics, showing correlations between regional solvation layer dynamics and protein dynamics in both aqueous and organic solvents. Correlations between protein flexibility and inverse solvent viscosity (1/η) are considered across several protein regions and for a rather disparate collection of solvents. It is seen that the correlation is consistently higher when local solvent shell dynamics are considered, rather than bulk viscosity. Protein flexibility is seen to correlate best with either the local interfacial viscosity or the ratio of the mobility of an organic solvent in a regional solvation layer relative to hydration dynamics around the same region. Results provide insight into the function of aqueous proteins, while also suggesting a framework for interpreting and predicting enzyme structural dynamics in non-aqueous solvents, based on the mobility of solvents within the solvation layer. We suggest that Kramers' theory may be used in future work to model protein conformational transitions in different solvents by incorporating local viscosity effects.</p

Molecular Modeling of Cetylpyridinium Bromide, a Cationic Surfactant, in Solutions and Micelle

Cationic surfactants are widely used in biological and industrial processes. Notably, surfactants with pyridinium salts, such as cetylpyridinium bromide (CPB), have diverse applications. The cetylpyridium cation has a quaternary nitrogen in the aromatic heterocyclic ring of the headgroup and 16 carbons in the hydrocarbon tail. At present and in the past, it has been widely used in germicides. Recently, several interesting applications of CPB have been explored, including its use in protein folding, polymerization, enzyme studies, and gene delivery as well as in pharmaceuticals as a drug delivery tool. A molecular-level understanding of CPB and its micelle in solution can enhance its development in such applications. Herein, we have proposed the first united-atom force field for CPB that yields stable micellar aggregates in molecular dynamics (MD) simulations. The force field is validated through classical MD simulations of the CPB monomer in pure water and 1-octanol as well as in an aqueous CPB micelle. We have performed principal component analysis (PCA) and calculated the translational and rotational diffusion coefficients, spatial distribution of solvent, counterion distribution, and rotational correlation time of CPB molecule in solutions and in micelle, comparing these data to previous experimental and theoretical results for a strong validation of the force field. PCA confirms that the pyridinium ring remains planar, whereas the movement of the hydrophobic tail region leads to conformational changes during the simulations. The collective modes of the pyridinum ring were identical for CPB molecule in solution and micelle, but conformational dynamics of the CPB tail were restricted in the micelle relative to motions in water and 1-octanol. Using this force field, a spherical CPB micelle was shown to be stable throughout the course of simulation, and its solvation and structural properties are characterized

High-Precision Megahertz-to-Terahertz Dielectric Spectroscopy of Protein Collective Motions and Hydration Dynamics

The low-frequency collective vibrational modes in proteins as well as the protein–water interface have been suggested as dominant factors controlling the efficiency of biochemical reactions and biological energy transport. It is thus crucial to uncover the mystery of the hydration structure and dynamics as well as their coupling to collective motions of proteins in aqueous solutions. Here, we report dielectric properties of aqueous bovine serum albumin protein solutions as a model system using an extremely sensitive dielectric spectrometer with frequencies spanning from megahertz to terahertz. The dielectric relaxation spectra reveal several polarization mechanisms at the molecular level with different time constants and dielectric strengths, reflecting the complexity of protein–water interactions. Combining the effective-medium approximation and molecular dynamics simulations, we have determined collective vibrational modes at terahertz frequencies and the number of water molecules in the tightly bound and loosely bound hydration layers. High-precision measurements of the number of hydration water molecules indicate that the dynamical influence of proteins extends beyond the first solvation layer, to around 7 Å distance from the protein surface, with the largest slowdown arising from water molecules directly hydrogen-bonded to the protein. Our results reveal critical information of protein dynamics and protein–water interfaces, which determine biochemical functions and reactivity of proteins