Location and Conformation of the LK alpha 14 Peptide in Water/Ethanol Mixtures

It is widely recognized that solvation is one of the major factors determining structure and functionality of proteins and long peptides, however it is a formidable challenge to address it both experimentally and computationally. For this reason, simple peptides are used to study fundamental aspects of solvation. It is well established that alcohols can change the peptide conformation and tuning of the alcohol content in solution can dramatically affect folding and, as a consequence, the function of the peptide. In this work, we focus on the leucine and lysine based LK alpha 14 peptide designed to adopt an alpha-helical conformation at an apolar-polar interface. We investigate LK alpha 14 peptide's bulk and interfacial behavior in water/ethanol mixtures combining a suite of experimental techniques (namely, circular dichroism and nuclear magnetic resonance spectroscopy for the bulk solution, surface pressure measurements and vibrational sum frequency generation spectroscopy for the air-solution interface) with molecular dynamics simulations. We observe that ethanol highly affects both the peptide location and conformation. At low ethanol content LK alpha 14 lacks a clear secondary structure in bulk and shows a clear preference to reside at the air-solution interface. When the ethanol content in solution increases, the peptide's interfacial affinity is markedly reduced and the peptide approaches a stable alpha-helical conformation in bulk facilitated by the amphiphilic nature of the ethanol molecules

消化器内科この一年

© the Owner Societies 2017.The influence of the amphiphile 1,3-dimethylurea (1,3-DMU) on the dynamic properties of water was studied using dielectric relaxation spectroscopy. The experiment provided evidence for substantial retardation of water reorientation in the hydration shell of 1,3-DMU, leading to a separate slow-water relaxation in addition to contributions from bulk-like and fast water as well as from the solute. From the amplitudes of the resolved water modes effective hydration numbers were calculated, showing that each 1,3-DMU molecule effectively freezes the reorientation of 1-2 water molecules. Additionally, a significant amount of solvent molecules, decreasing from ∼39 at infinite dilution to ∼3 close to the solubility limit, is retarded by a factor of ∼1.4 to 2.3, depending on concentration. The marked increase of the solute amplitude indicates pronounced parallel dipole alignment between 1,3-DMU and its strongly bound H2O molecules. Molecular dynamics (MD) simulations of selected solutions revealed a notable slowdown of water rotation for those solvent molecules surrounding the methyl groups of 1,3-DMU and strong binding of ∼2H2O by the hydrophilic carbonyl group, corroborating thus the experimental results. Additionally, the simulations revealed 1,3-DMU self-aggregates of substantial lifetime

Hydration and self-aggregation of a neutral cosolute from dielectric relaxation spectroscopy and MD simulations: The case of 1,3-dimethylurea

© the Owner Societies 2017.The influence of the amphiphile 1,3-dimethylurea (1,3-DMU) on the dynamic properties of water was studied using dielectric relaxation spectroscopy. The experiment provided evidence for substantial retardation of water reorientation in the hydration shell of 1,3-DMU, leading to a separate slow-water relaxation in addition to contributions from bulk-like and fast water as well as from the solute. From the amplitudes of the resolved water modes effective hydration numbers were calculated, showing that each 1,3-DMU molecule effectively freezes the reorientation of 1-2 water molecules. Additionally, a significant amount of solvent molecules, decreasing from ∼39 at infinite dilution to ∼3 close to the solubility limit, is retarded by a factor of ∼1.4 to 2.3, depending on concentration. The marked increase of the solute amplitude indicates pronounced parallel dipole alignment between 1,3-DMU and its strongly bound H2O molecules. Molecular dynamics (MD) simulations of selected solutions revealed a notable slowdown of water rotation for those solvent molecules surrounding the methyl groups of 1,3-DMU and strong binding of ∼2H2O by the hydrophilic carbonyl group, corroborating thus the experimental results. Additionally, the simulations revealed 1,3-DMU self-aggregates of substantial lifetime

Water slippage versus contact angle: a quasiuniversal relationship

Using molecular dynamics simulations of an atomistic water model, we study the interfacial hydrodynamic slippage of water at various hydrophobic surfaces, both organic (silane monolayers) and inorganic (diamondlike and Lennard-Jones models). The measured slip lengths range from nanometers to tens of nanometers. Slip lengths on different surfaces are found to collapse nearly onto a single curve as a function of the static contact angle characterizing the surface wettability, thereby suggesting a quasiuniversal relationship. This dependence is rationalized on the basis of a simple scaling description of the fluid-solid friction at the microscopic level. The link between slippage and water depletion at hydrophobic surfaces is clarified. These results shed light on the controversy over experimental measurements of the slip length at smooth hydrophobic surfaces.David M. Huang, Christian Sendner, Dominik Horinek, Roland R. Netz and Lydéric Bocque

The Interplay of Methyl-Group Distribution and Hydration Pattern of Isomeric Amphiphilic Osmolytes

© 2018 American Chemical Society. The intermolecular interactions and dynamics of aqueous 1,1-dimethyurea (1,1-DMU) solutions were studied by examining the concentration dependence of the solvent and solute relaxations detected by dielectric spectroscopy. Molecular dynamics simulations were carried out to facilitate interpretation of the dielectric data and to get a deeper insight into the behavior of the system components at the microscopic level. In particular, the simulations allowed for explaining the main differences between the dielectric spectra of aqueous solutions of 1,1-DMU and of its structural isomer 1,3-DMU. Similar to the previously studied compounds urea and 1,3-DMU, 1,1-DMU forms rather stable hydrates. This is evidenced by an effective solute dipole moment that significantly exceeds the value of a neat 1,1-DMU molecule, indicating pronounced parallel alignment of the solute dipole with two to three H2O moments. The MD simulations revealed that the involved water molecules form strong hydrogen bonds with the carbonyl group. However, in contrast to 1,3-DMU, it was not possible to resolve a "slow-water" mode in the dielectric spectra, suggesting rather different hydration-shell dynamics for 1,1-DMU as confirmed by the simulations. In contrast to aqueous urea and 1,3-DMU, addition of 1,1-DMU to water leads to a weak decrease of the static permittivity. This is explained by the emergence of antiparallel dipole-dipole correlations among 1,1-DMU hydrates with rising concentration

Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins

Water and water-mediated interactions determine thermodynamic and kinetics of protein folding, protein aggregation and self-assembly in confined spaces. To obtain insights into the role of water in the context of folding problems, we describe computer simulations of a few related model systems. The dynamics of collapse of eicosane shows that upon expulsion of water the linear hydrocarbon chain adopts an ordered helical hairpin structure with 1.5 turns. The structure of dimer of eicosane molecules has two well ordered helical hairpins that are stacked perpendicular to each other. As a prelude to studying folding in confined spaces we used simulations to understand changes in hydrophobic and ionic interactions in nano droplets. Solvation of hydrophobic and charged species change drastically in nano water droplets. Hydrophobic species are localized at the boundary. The tendency of ions to be at the boundary where water density is low increases as the charge density decreases. Interaction between hydrophobic, polar, and charged residue are also profoundly altered in confined spaces. Using the results of computer simulations and accounting for loss of chain entropy upon confinement we argue and then demonstrate, using simulations in explicit water, that ordered states of generic amphiphilic peptide sequences should be stabilized in cylindrical nanopores

Level-Set Variational Implicit-Solvent Modeling of Biomolecules with the Coulomb-Field Approximation

Central in the variational implicit-solvent model (VISM) [Dzubiella, Swanson, and McCammon Phys. Rev. Lett.2006, 96, 087802 and J. Chem. Phys.2006, 124, 084905] of molecular solvation is a mean-field free-energy functional of all possible solute–solvent interfaces or dielectric boundaries. Such a functional can be minimized numerically by a level-set method to determine stable equilibrium conformations and solvation free energies. Applications to nonpolar systems have shown that the level-set VISM is efficient and leads to qualitatively and often quantitatively correct results. In particular, it is capable of capturing capillary evaporation in hydrophobic confinement and corresponding multiple equilibrium states as found in molecular dynamics (MD) simulations. In this work, we introduce into the VISM the Coulomb-field approximation of the electrostatic free energy. Such an approximation is a volume integral over an arbitrary shaped solvent region, requiring no solutions to any partial differential equations. With this approximation, we obtain the effective boundary force and use it as the “normal velocity” in the level-set relaxation. We test the new approach by calculating solvation free energies and potentials of mean force for small and large molecules, including the two-domain protein BphC. Our results reveal the importance of coupling polar and nonpolar interactions in the underlying molecular systems. In particular, dehydration near the domain interface of BphC subunits is found to be highly sensitive to local electrostatic potentials as seen in previous MD simulations. This is a first step toward capturing the complex protein dehydration process by an implicit-solvent approach

Interactions of the Apolipoprotein A5 Gene Polymorphisms and Alcohol Consumption on Serum Lipid Levels

Little is known about the interactions of apolipoprotein (Apo) A5 gene polymorphisms and alcohol consumption on serum lipid profiles. The present study was undertaken to detect the interactions of ApoA5-1131T>C, c.553G>T and c.457G>A polymorphisms and alcohol consumption on serum lipid levels.A total of 516 nondrinkers and 514 drinkers were randomly selected from our previous stratified randomized cluster samples. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. The levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P<0.05-0.001). The genotypic and allelic frequencies of three loci were not different between the two groups. The interactions between -1131T>C genotypes and alcohol consumption on ApoB levels (P<0.05) and the ApoA1/ApoB ratio (P<0.01), between c.553G>T genotypes and alcohol consumption on low-density lipoprotein cholesterol (LDL-C) levels (P<0.05) and the ApoA1/ApoB ratio (P<0.05), and between c.457G>A genotypes and alcohol consumption on TG levels (P<0.001) were detected by factorial regression analysis after controlling for potential confounders. Four haplotypes (T-G-G, C-G-G, T-A-G and C-G-T) had frequencies ranging from 0.06 to 0.87. Three haplotypes (C-G-G, T-A-G, and C-G-T) were significantly associated with serum lipid parameters. The -1131T>C genotypes were correlated with TG, and c.553G>T and c.457G>A genotypes were associated with HDL-C levels in nondrinkers (P<0.05 for all). For drinkers, the -1131T>C genotypes were correlated with TC, TG, LDL-C, ApoB levels and the ApoA1/ApoB ratio (P<0.01 for all); c.553G>T genotypes were correlated with TC, TG, HDL-C and LDL-C levels (P<0.05-0.01); and c.457G>A genotypes were associated with TG, LDL-C, ApoA1 and ApoB levels (P<0.05-0.01).The differences in some serum lipid parameters between the drinkers and nondrinkers might partly result from different interactions of the ApoA5 gene polymorphisms and alcohol consumption