PubChemSR: A search and retrieval tool for PubChem

Background  

Recent years have seen an explosion in the amount of publicly available chemical and related biological information. A significant step has been the emergence of PubChem, which contains property information for millions of chemical structures, and acts as a repository of compounds and bioassay screening data for the NIH Roadmap. There is a strong need for tools designed for scientists that permit easy download and use of these data. We present one such tool, PubChemSR.     

Identification of critical residues in loop E in the 5-HT3ASR binding site

Background  

The serotonin type 3 receptor (5-HT₃R) is a member of a superfamily of ligand gated ion channels. All members of this family share a large degree of sequence homology and presumably significant structural similarity. A large number of studies have explored the structure-function relationships of members of this family, particularly the nicotinic and GABA receptors. This information can be utilized to gain additional insights into specific structural and functional features of other receptors in this family.     

Automated extraction of chemical structure information from digital raster images

Background  

To search for chemical structures in research articles, diagrams or text representing molecules need to be translated to a standard chemical file format compatible with cheminformatic search engines. Nevertheless, chemical information contained in research articles is often referenced as analog diagrams of chemical structures embedded in digital raster images. To automate analog-to-digital conversion of chemical structure diagrams in scientific research articles, several software systems have been developed. But their algorithmic performance and utility in cheminformatic research have not been investigated.     

Binding specificity of Bacillus thuringiensis Cry1Aa for purified, native Bombyx mori aminopeptidase N and cadherin-like receptors

Background  

To better understand the molecular interactions of Bt toxins with non-target insects, we have examined the real-time binding specificity and affinity of Cry1 toxins to native silkworm (Bombyx mori) midgut receptors. Previous studies on B. mori receptors utilized brush border membrane vesicles or purifed receptors in blot-type assays.     

Glycosaminoglycans in human retinoblastoma cells: Heparan sulfate,a modulator of the pigment epithelium-derived factor-receptor interactions

Background  

Pigment epithelium-derived factor (PEDF) has binding affinity for cell-surface receptors in retinoblastoma cells and for glycosaminoglycans. We investigated the effects of glycosaminoglycans on PEDF-receptor interactions.     

The acidic domains of the Toc159 chloroplast preprotein receptor family are intrinsically disordered protein domains

Background  

The Toc159 family of proteins serve as receptors for chloroplast-destined preproteins. They directly bind to transit peptides, and exhibit preprotein substrate selectivity conferred by an unknown mechanism. The Toc159 receptors each include three domains: C-terminal membrane, central GTPase, and N-terminal acidic (A-) domains. Although the function(s) of the A-domain remains largely unknown, the amino acid sequences are most variable within these domains, suggesting they may contribute to the functional specificity of the receptors.     

Chemogenetic fingerprinting by analysis of cellular growth dynamics

Background  

A fundamental goal in chemical biology is the elucidation of on- and off-target effects of drugs and biocides. To this aim chemogenetic screens that quantify drug induced changes in cellular fitness, typically taken as changes in composite growth, is commonly applied.     

Identification of a Bacillus thuringiensis Cry11Ba toxin-binding aminopeptidase from the mosquito, Anopheles quadrimaculatus

Background  

Aminopeptidase N (APN) type proteins isolated from several species of lepidopteran insects have been implicated as Bacillus thuringiensis (Bt) toxin-binding proteins (receptors) for Cry toxins. We examined brush border membrane vesicle (BBMV) proteins from the mosquito Anopheles quadrimaculatus to determine if APNs from this organism would bind mosquitocidal Cry toxins that are active to it.     

Charting calcium-regulated apoptosis pathways using chemical biology: role of calmodulin kinase II

Background  

Intracellular free calcium ([Ca²⁺]_i) is a key element in apoptotic signaling and a number of calcium-dependent apoptosis pathways have been described. We here used a chemical biology strategy to elucidate the relative importance of such different pathways.     

Enhancement of intracellular γ-tocopherol levels in cytokine-stimulated C3H 10T1/2 fibroblasts: relation to NO synthesis,isoprostane formation,and tocopherol oxidation

Background  

Stimulation of C3H 10T1/2 murine fibroblasts with interferon-γ(IFN) and bacterial lipopolysaccharide (LPS) generates reactive oxygen and nitrogen species leading to DNA damage, lipid oxidation, and tocopherol oxidation. The tocopherols possess unique chemical and biological properties that suggest they have important roles related to intracellular defense against radical-mediated damage.     

DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening

Background  

Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats.     

The evolution of farnesoid X,vitamin D,and pregnane X receptors: insights from the green-spotted pufferfish (<Emphasis Type="Italic">Tetraodon nigriviridis</Emphasis>) and other non-mammalian species

Background  

The farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor (VDR) are three closely related nuclear hormone receptors in the NR1H and 1I subfamilies that share the property of being activated by bile salts. Bile salts vary significantly in structure across vertebrate species, suggesting that receptors binding these molecules may show adaptive evolutionary changes in response. We have previously shown that FXRs from the sea lamprey (Petromyzon marinus) and zebrafish (Danio rerio) are activated by planar bile alcohols found in these two species. In this report, we characterize FXR, PXR, and VDR from the green-spotted pufferfish (Tetraodon nigriviridis), an actinopterygian fish that unlike the zebrafish has a bile salt profile similar to humans. We utilize homology modelling, docking, and pharmacophore studies to understand the structural features of the Tetraodon receptors.     

Calculation of chemical shielding in C-doped zigzag BN nanotubes

Abstract  

Chemical shielding tensors at the sites of various ¹¹B and ¹⁵N nuclei were calculated to study the electronic structure properties of carbon-doped boron nitride nanotubes. The chemical shielding tensors were converted to isotropic and anisotropic chemical shielding parameters. The results reveal the significant effect of C-doping on the chemical shielding tensors at the sites of those ¹¹B and ¹⁵N nuclei located in the nearest neighborhood of the C-doped ring. The isotropic and anisotropic chemical shielding tensors of those B atoms directly bonded to C atoms reach values observed for B atoms placed at the B-mouth of the nanotube.     

Interplay of thermochemistry and Structural Chemistry, the journal (volume 17, 2006) and the discipline

Abstract  

In the current study we relate the contents of the journal of “Structural Chemistry” for the calendar year 2006 to thermochemistry. Each paper is briefly summarized and supplemented by a comment which explicitly interrelates the content of the study to chemical energetics.     

Fast 3D shape screening of large chemical databases through alignment-recycling

Background  

Large chemical databases require fast, efficient, and simple ways of looking for similar structures. Although such tasks are now fairly well resolved for graph-based similarity queries, they remain an issue for 3D approaches, particularly for those based on 3D shape overlays. Inspired by a recent technique developed to compare molecular shapes, we designed a hybrid methodology, alignment-recycling, that enables efficient retrieval and alignment of structures with similar 3D shapes.     

Thermal stability,pH dependence and inhibition of four murine kynurenine aminotransferases

Background  

Kynurenine aminotransferase (KAT) catalyzes the transamination of kynunrenine to kynurenic acid (KYNA). KYNA is a neuroactive compound and functions as an antagonist of alpha7-nicotinic acetylcholine receptors and is the only known endogenous antagonist of N-methyl-D-aspartate receptors. Four KAT enzymes, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase, have been reported in mammalian brains. Because of the substrate overlap of the four KAT enzymes, it is difficult to assay the specific activity of each KAT in animal brains.     

Calculated conformer energies for organic molecules with multiple polar functionalities are method dependent: Taxol (case study)

Background  

Molecular mechanics (MM) and quantum chemical (QM) calculations are widely applied and powerful tools for the stereochemical and conformational investigations of molecules. The same methods have been extensively used to probe the conformational profile of Taxol (Figure 1) both in solution and at the β-tubulin protein binding site.     

Pybel: a Python wrapper for the OpenBabel cheminformatics toolkit

Background  

Scripting languages such as Python are ideally suited to common programming tasks in cheminformatics such as data analysis and parsing information from files. However, for reasons of efficiency, cheminformatics toolkits such as the OpenBabel toolkit are often implemented in compiled languages such as C++. We describe Pybel, a Python module that provides access to the OpenBabel toolkit.     

The effect of ultrasonic pre-treatment on the catalytic activity of lipases in aqueous and non-aqueous media

Background  

Ultrasound has been used to accelerate the rates of numerous chemical reactions, however its effects on enzymatic reactions have been less extensively studied. While known to result in the acceleration of enzyme-catalysed reactions, ultrasonication has also been shown to induce enzyme inactivation. In this study we investigated the effects of ultrasonic pretreatment on lipases in both aqueous and non-aqueous media.     

Facile solution-phase synthesis of γ-Mn3O4 hierarchical structures

Background  

A lot of effort has been focused on the integration of nanorods/nanowire as building blocks into three-dimensional (3D) complex superstructures. But, the development of simple and effective methods for creating novel assemblies of self-supported patterns of hierarchical architectures to designed materials using a suitable chemical method is important to technology and remains an attractive, but elusive goal.