Molecular Theory of Hydration at Different Temperatures

Solvation plays an important role in diverse chemical processes ranging from reaction kinetics to molecular recognition, solubility, and phase separations. Despite a long-history of theoretical exploration, quantitative prediction of solvation remains a theoretical challenge without relying on the macroscopic properties of the solvent as an input. Here we present a molecular density functional theory that provides a self-consistent description of the solvation structure and thermodynamic properties of small organic molecules in liquid water at different temperatures. Based on the solute configuration and force-field parameters generated from first-principles calculations, the theoretical predictions are found in good agreement with experimental data for the hydration free energies of 197 organic molecules in a temperature range from 0 to 40 °C. In addition to calibration with experimental results, the theoretical predictions are compared with recent molecular dynamics simulations for the hydration of five highly explosive nitrotoluenes. This work demonstrates the potential of the classical density functional theory for high-throughput prediction of solvation properties over a broad range of temperatures

Solvation Structure of Surface-Supported Amine Fragments: A Molecular Dynamics Study

Amine-grafted silica gel is an efficient heterogeneous catalyst for the Knoevenagel condensation and draws much attention in green chemistry for applications like heavy metal adsorption and CO₂ fixation. Despite its successful usage in diverse areas, fundamental questions remain on how the silica substrate affects the local chemical environment of the tethered amines. In this work, we use all-atom molecular dynamics simulation to investigate the solvation structures of two primary amines tethered onto a silica surface at different pHs of aqueous solutions. The atomic density profiles in the solvation shell are analyzed with a spherical harmonics expansion method for both isolated and silica-supported amines in different aqueous environments. The simulation results provide direct evidence for the strong influence of the silica surface on the hydration structure that is often ignored in the theoretical analysis of surface reactions. The surface effect becomes less prominent on the tethered amine as the alkyl chain length increases

A hypothetical model for maspin as a prognostic marker of ESCC.

<p>A hypothetical model for maspin as a prognostic marker of ESCC.</p

Characterization of stably transfected KYSE510 cell lines.

<p>(A) Western blotting of maspin and housekeeping protein β-actin in the total lysates of parental KYSE510, M-KYSE510, and V-KYSE510 cells. (B) MTT assay of the proliferation of parental KYSE510, M-KYSE510, and V-KYSE510 cells, cultured in the maintenance media. (C) Representative staining of single cell-derived colonies (bottom) and the magnified image of the highlighted colonies (top) from the colony formation assay. (D) Quantification of colonies with more than >100 cells/colony based on counting under microscope in the colony formation assay. Data represent the average of three independent repeats. Error bars represent the standard deviation. The difference between M-KYSE51 and V-KYSE510 (or parental KYSE510) was statistically significant (<i>p</i><0.001).</p

Kaplan-Meier survival curves of ESCC.

<p>(A) Cases stratified based on the overall maspin expression, (B) levels of maspin staining in the nucleus, and (C) the levels of maspin expression in the cytoplasm.</p

The effects of maspin expression on cell motility and invasion.

<p>(A) Representative microscopic images of post-wounding monolayer cell culture at the indicated time points. (B) Representative microscopic images of the underside of the transwell invasion assay membrane. (C) Quantification of the number of invasive cells based on the counting of the invading cells shown in (B). M-KYSE510 showed significantly lower numbers of invasive cells. Data represent the average of three independent repeats. Error bars represent the standard deviations.</p

Correlation of ESCC Clinicopathological Features with Maspin Expression and Subcellular Localization.

<p>Correlation of ESCC Clinicopathological Features with Maspin Expression and Subcellular Localization.</p

The correlation of maspin expression in established human ESCC cell lines with lower rates of proliferation <i>in vitro</i>.

<p>(A) Western blotting of maspin in the indicated ESCC cell lines. Twenty-five micrograms of total lysate protein were loaded in each lane. Western blotting of the same membrane for house-keeping β-actin was used to assess the loading variation. (B) MTT assay of the proliferation of ESCC cell lines. The data at each time point represent the average of three independent repeats. The error bars represent the standard deviation.</p

Identification of an Intrinsic Determinant Critical for Maspin Subcellular Localization and Function

<div><p>Maspin, a multifaceted tumor suppressor, belongs to the serine protease inhibitor superfamily, but only inhibits serine protease-like enzymes such as histone deacetylase 1 (HDAC1). Maspin is specifically expressed in epithelial cells and it is differentially regulated during tumor progression. A new emerging consensus suggests that a shift in maspin subcellular localization from the nucleus to the cytoplasm stratifies with poor cancer prognosis. In the current study, we employed a rational mutagenesis approach and showed that maspin reactive center loop (RCL) and its neighboring sequence are critical for maspin stability. Further, when expressed in multiple tumor cell lines, single point mutation of Aspartate³⁴⁶ (D³⁴⁶) to Glutamate (E³⁴⁶), maspin^D346E, was predominantly nuclear, whereas wild type maspin (maspin^WT) was both cytoplasmic and nuclear. Evidence from cellular fractionation followed by immunological and proteomic protein identification, combined with the evidence from fluorescent imaging of endogenous proteins, fluorescent protein fusion constructs, as well as bimolecular fluorescence complementation (BiFC) showed that the increased nuclear enrichment of maspin^D346E was, at least in part, due to its increased affinity to HDAC1. Maspin^D346E was also more potent than maspin^WT as an HDAC inhibitor. Taken together, our evidence demonstrates that D³⁴⁶ is a critical <i>cis</i>-element in maspin sequence that determines the molecular context and subcellular localization of maspin. A mechanistic model derived from our evidence suggests a new window of opportunity for the development of maspin-based biologically competent HDAC inhibitors for cancer treatment.</p></div

Structural comparison of PDZ domains.

<p>(A) Superposition of the structures of PDZ1-CXCR2 (purple; PDB code: 4JL7), PDZ1-CFTR (orange; PDB code: 1I92) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076219#B12" target="_blank">12</a>], PDZ1-2AR (cyan; PDB code: 1GQ4) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076219#B13" target="_blank">13</a>], and PDZ1-PDGFR (yellow; PDB code: 1GQ5) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076219#B13" target="_blank">13</a>]. PDZ domains are represented by ribbon, while residues in the ligands are displayed as sticks. (B) Superposition of the PDZ1 ligand binding pockets. Both PDZ1 and ligand residues are depicted by sticks and colored according to the scheme in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076219#pone-0076219-g003" target="_blank">Figure 3A</a>. (C) Close-up views of structural differences of His29 (top) and Arg40 (bottom). The CXCR2 peptide is depicted by sticks overlaid with 2Fo − Fc omit map calculated at 1.16 Å and contoured at 2.0 σ. (D) Superposition of NHERF1 PDZ1 (purple) and PDZ2 (pink; PDB code: 2OZF) peptide binding pockets. CXCR2 peptide is shown in green and PDZ residues are depicted by balls-and-sticks.</p