Hydrogen Bond Acceptor (hydrogen + bond_acceptor)

Distribution by Scientific Domains


Selected Abstracts


Quantitative Structure,Activity Relationship Studies for the Binding Affinities of Imidazobenzodiazepines for the ,6 Benzodiazepine Receptor Isoform Utilizing Optimized Blockwise Variable Combination by Particle Swarm Optimization for Partial Least Squares Modeling

MOLECULAR INFORMATICS, Issue 1 2007
Leqian Hu
Abstract Binding affinities of a series of substituted imidazobenzodiazepines for the ,6 Benzodiazepine Receptor (BzR) isoform are investigated by the Optimized Blockwise Variable Combination (OBVC) by Particle Swarm Optimization (PSO) based on Partial Least Squares (PLS) modeling. The QSAR analysis result showed that MolRef, AlogP, MRCM**-3, Rotatable bonds (Rotlbonds), Hydrogen Bond Acceptors (Hbond acceptor), five Jurs descriptors, two Shadow indices descriptors and principal moment of inertia are the most important descriptors among all the investigated descriptors. One can change the molar refractivity, the polar interactions between molecules, the shape of the molecules, the principal moments of inertia about the principal axes of a molecule, the hydrophobic character of the molecule, the number of Rotlbonds and Hbond acceptors of the compounds to adjust the binding affinities of imidazobenzodiazepine for the ,6 BzR isoform. The Quantitative Structure,Activity Relationship (QSAR) analysis result was also compared with MLR, PLS, and hierarchical PLS algorithms. It has been demonstrated that OBVC by PSO for PLS modeling shows satisfactory performance in the QSAR analysis. [source]


Oxidation of substituted benzaldehydes by quinolinium chlorochromate: A structure and solvent dependent kinetic study

INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2003
G. Fatima Jeyanthi
The kinetics of oxidation of several para-substituted benzaldehydes by quinolinium chlorochromate was studied under pseudo-first-order conditions in different (hydrogen bond donor and hydrogen bond acceptor) neat organic solvents. The operation of nonspecific and specific solvent,solvent,solute interactions was explored by correlating the rate data with solvent parameters through correlation analysis. Both electron-releasing and electron-withdrawing substituents enhanced the rate and the Hammett plot showed a break in the reactivity order indicating applicability of dual mechanism. An explanation in conformity with structure and solvent effects on reactivity has been proposed. 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 154,158, 2003 [source]


Generation of Selective TACE Inhibitors: Ligand and Structure Based Molecular Modeling, Virtual Screening, Counter Pharmacophore Screening to Get Selective Molecules

MOLECULAR INFORMATICS, Issue 11-12 2009
Malkeet, Singh Bahia
Abstract This study describes the ligand based as well as structure based molecular modeling and virtual screening of selective tumor necrosis factor-, converting enzyme (TACE) inhibitors. In ligand based molecular modeling, two statistically reliable pharmacophore models HypoA1 and HypoB1 were generated using a same training set of 22,molecules. HypoA1,consists of two hydrogen bond acceptor and three hydrophobic groups whereas HypoB1 consists of one hydrogen bond donor, one ring aromatic and three hydrophobic groups. Virtual screening was performed with both models in in-house database of 1.2,million molecules. To remove non selective hits from screened molecules, a counter pharmacophore was generated using inhibitors of MMP-1, an important enzyme involved in musculoskeletal degradation. In structure based molecular modeling, docking analysis was performed to explore the important interactions between ligands and protein. On comparison, HypoA1 and HypoB1 were found to be complementing with results of docking analysis suggesting high reliability of both models for their use in virtual screening/designing of new molecules. [source]


Mining protein dynamics from sets of crystal structures using "consensus structures"

PROTEIN SCIENCE, Issue 4 2010
Gerard J. P. van Westen
Abstract In this work, we describe two novel approaches to utilize the dynamic structure information implicitly contained in large crystal structure data sets. The first approach visualizes both consistent as well as variable ligand-induced changes in ligand-bound compared with apo protein crystal structures. For this purpose, information was mined from B-factors and ligand-induced residue displacements in multiple crystal structures, minimizing experimental error and noise. With this approach, the mechanism of action of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as an inseparable combination of distortion of protein dynamics and conformational changes of HIV-1 reverse transcriptase was corroborated (a combination of the previously proposed "molecular arthritis" and "distorted site" mechanisms). The second approach presented here uses "consensus structures" to map common binding features that are present in a set of structures of NNRTI-bound HIV-1 reverse transcriptase. Consensus structures are based on different levels of structural overlap of multiple crystal structures and are used to analyze protein,ligand interactions. The structures are shown to yield information about conserved hydrogen bonding interactions as well as binding-pocket flexibility, shape, and volume. From the consensus structures, a common wild type NNRTI binding pocket emerges. Furthermore, we were able to identify a conserved backbone hydrogen bond acceptor at P236 and a novel hydrophobic subpocket, which are not yet utilized by current drugs. Our methods introduced here reinterpret the atom information and make use of the data variability by using multiple structures, complementing classical 3D structural information of single structures. [source]


Vibrational coupling as diagnostic for intramolecular hydrogen bonds of carbohydrates in aqueous solution

BIOPOLYMERS, Issue 1 2002
Pedro Carmona
Abstract The coupling of ,CO and ,OD vibrations in the 1200,900 cm,1 IR range leads to band shifting in opposite directions, which provides information on intramolecular hydrogen bonding of carbohydrates in aqueous solution. The aqueous solution IR spectra of 2-acetamide-1,6-anhydro-2-deoxy- D -glucopyranose and cis-1,2-cyclopentanediol and tetrahydrofuran,ethanol mixtures are reported. Frequency upshifting upon deuteration is observed for the ,CO bands of both a hydrogen bond acceptor and donor in ether,hydroxyl and hydroxyl,hydroxyl contacts. The 1200,900 cm,1 range can be used to reveal the presence of intramolecular hydrogen bonds in aqueous carbohydrates, unlike the OH stretching region, which cannot be used in this sense due to carbohydrate band masking by the strong ,OH IR absorption of water. 2002 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 67: 20,25, 2002; DOI 10.1002/bip.10024 [source]


Insight into the Bioactivity and Metabolism of Human Glucagon Receptor Antagonists from 3D-QSAR Analyses

MOLECULAR INFORMATICS, Issue 8 2004
HaiFeng Chen
Abstract Descriptors, such as logP, the number of hydrogen bond donors, the number of hydrogen bond acceptors, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) combined with fields of CoMFA and CoMSIA to construct models for hyperglycemia decrease activity and metabolism of human glucagon receptor antagonists. The results reveal that including logP, HOMO and LUMO energies is meaningful for QSAR/QSMR model. The models were validated by using a test set of structural diverse compounds that had not been included in the CoMFA and CoMSIA models. Support Vector Machines (SVM) have been used to select the suitable additional descriptors to construct 3D-QSAR/QSMR models. A key factor to mention is that activity and metabolism models simultaneously. These in silico ADME models are helpful in making quantitative prediction of inhibitory activities and rates of metabolism before resorting in vitro and in vivo experimentation. [source]


Cross-linked agarose for separation of low molecular weight natural products in hydrophilic interaction liquid chromatography

BIOTECHNOLOGY JOURNAL, Issue 5 2010
Tianwei Tan
Abstract Following its market introduction in 1982, the cross-linked 12% agarose gel media Superose 12 has become widely known as a tool for size exclusion chromatography of proteins and other biological macromolecules. In this review it is shown that, when appropriate mobile phases are used, Superose possesses adsorption properties similar to that of traditional media for hydrophilic interaction liquid chromatography (HILIC). This is illustrated by the separation and purification of low molecular weight compounds such as polyphenols including active components of traditional Chinese medicinal herbs and green tea. Structural features of the cross-linked agarose that likely cause the observed adsorption effects are discussed aswell. These are identified as being primarily ether bonds acting as strong hydrogen bond acceptors as well as hydrophobic residues originating from the cross-linking reagents. [source]


Measured and calculated CD spectra of G-quartets stacked with the same or opposite polarities,,

CHIRALITY, Issue 3-4 2008
Donald M. Gray
Abstract Circular dichroism (CD) spectroscopy is widely used to characterize the structures of DNA G-quadruplexes. CD bands at 200,300 nm have been empirically related to G-quadruplexes having parallel or antiparallel sugar-phosphate backbones. We propose that a more fundamental interpretation of the origin of the CD bands is in the stacking interactions of neighboring G-quartets, which can have the same or opposing polarities of hydrogen bond acceptors and donors. From an empirical summation of CD spectra of the d(G)5 G-quadruplex and of the thrombin binding aptamer that have neighboring G-quartets with the same and opposite polarities, respectively, the spectra of aptamers selected by the Ff gene 5 protein (g5p) appear to arise from a combination of the two types of polarities of neighboring G-quartets. The aptamer CD spectra resemble the spectrum of d(G3T4G3), in which two adjacent quartets have the same and two have opposite polarities. Quantum-chemical spectral calculations were performed using a matrix method, based on guanine chromophores oriented as in d(G3T4G3). The calculations show that the two types of G-quartet stacks have CD spectra with features resembling experimental spectra of the corresponding types of G-quadruplexes. Chirality, 2008. 2007 Wiley-Liss, Inc. [source]