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DNA methylation status may be used as a functional indicator of moderately depleted folate status. The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women.

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Explicit solvent all-atom molecular dynamics simulations of mixtures of poly(styrenesulfonate)-(PSS) and poly(diallyldimethylammonium) (PDADMA) polyelectrolytes at various salt (NaCl) concentrations are performed. We characterize the formed polyelectrolyte complexes (PECs) and relate the observed physical properties of PSS-PDADMA PECs to the properties found in polyelectrolyte multilayers (PEMs) made of the same compositions. Our results reveal a change in the way charges are compensated upon the addition of salt, namely from an intrinsic mechanism (polyanions pair with polycations) toward an extrinsic one (polyions pair with salt ions). The probability of the intrinsic compensating mechanism decreases from about 90% to about 60% when the salt concentration increases from 0.168 to 1 mol/L. The interaction energies of the ion-pairing follow the order of Na-Cl>PSS-Na>PDADMA-Cl=PSS-PDADMA. Furthermore, we investigate thoroughly the water distribution and study the hydration mechanisms in our system. Water is found to be homogeneously distributed inside our investigated systems, while we find a negligible difference between the hydration ability of (PDADMA þ Cl -) and (PSS þ Na þ ). This lack of asymmetric behavior demonstrates that the observed swelling-shrinking switch during the buildup of PEMs cannot be related to the hydration behavior, and we suggest that the presence of a substrate has to play a critical role. A further analysis of the water structure shows that the dielectric constant inside such mixtures is roughly 1 order of magnitude lower than in bulk water, and our determined values compare favorably with experimental measurements. Finally the diffusion of water molecules inside the PE mixtures is found to be 2 orders of magnitude slower than that in pure water.

We introduce a regularization procedure to define electrostatic energies and forces in a slab system of thickness h that is periodic in two dimensions and carries a net charge. The regularization corresponds to a neutralization of the system by two charged walls and can be viewed as the extension to the two-dimensional (2D)+h geometry of the neutralization by a homogeneous background in the standard three-dimensional Ewald method. The energies and forces can be computed efficiently by using advanced methods for systems with 2D periodicity, such as MMM2D or P3M/ELC, or by introducing a simple background-charge correction to the Yeh-Berkowitz approach of slab systems. The results are checked against direct lattice sum calculations on simple systems. We show, in particular, that the Madelung energy of a 2D square charge lattice in a uniform compensating background is correctly reproduced to high accuracy. A molecular dynamics simulation of a sodium ion close to an air/water interface is performed to demonstrate that the method does indeed provide consistent long-range electrostatics. The mean force on the ion reduces at large distances to the image-charge interaction predicted by macroscopic electrostatics. This result is used to determine precisely the position of the macroscopic dielectric interface with respect to the true molecular surface.

An extension to the P(3)M algorithm for electrostatic interactions is presented that allows to efficiently compute dipolar interactions in periodic boundary conditions. Theoretical estimates for the root-mean-square error of the forces, torques, and the energy are derived. The applicability of the estimates is tested and confirmed in several numerical examples. A comparison of the computational performance of the new algorithm to a standard dipolar-Ewald summation methods shows a performance crossover from the Ewald method to the dipolar P(3)M method for as few as 300 dipolar particles. In larger systems, the new algorithm represents a substantial improvement in performance with respect to the dipolar standard Ewald method. Finally, a test comparing point-dipole-based and charged-pair based models shows that point-dipole-based models exhibit a better performance than charged-pair based models.

Human aquaporin-1 (hAQP1) is a water channel found in many tissues and potentially involved in several human pathologies. Selective inhibitors of hAQP1 are discussed as novel treatment opportunities for glaucoma, brain edema, inflammatory pain, and certain types of cancer. However, only very few potent and chemically attractive blockers have been reported to date. In this study we present three novel hAQP1 blockers that have been identified by virtual screening and inhibit water flux through hAQP1 in Xenopus laevis oocyte swelling assays at low micromolar concentrations. The newly discovered compounds display no chemical similarity to hitherto known hAQP1 blockers and bind at the extracellular entrance of the channel, close to the ar/R selectivity filter. Futhermore, mutagenesis studies showed that Lys36, which is not conserved among the hAQP family, is crucially involved in binding and renders the discovered compounds suitable as leads for the development of selective hAQP1 inhibitors.A quaporins (AQPs) are passive membrane channels that, in many species, facilitate highly efficient yet strictly selective permeation of water and small solutes across lipid bilayers. AQPs can be divided into two major subclasses, the aquaporin subfamiliy that selectively transports water and the aquaglyceroporin family that in addition transports small uncharged molecules such as glycerol.

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