SEARCH · PubMed Health

Results for “Models, Chemical”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed2002

Bioinformatics and molecular modeling in chemical enzymology. Active sites of hydrolases.

Comparison and multiple alignments of amino acid sequences of a representative number of related enzymes demonstrate the existence of certain positions of amino acid residues which are permanently reproducible in all members of the whole family. The use of the bioinformatic approach revealed conservative residues in each of the related enzymes and ranked amino acid conservatism for the overall enzymatic catalysis. Glycine and aspartic acid residues were shown to be the most essential for structure and catalytic activity of enzymes. Amino acid residues forming catalytic subsite of the active site of enzymes are always highly conservative. Analysis revealed that aspartic acid carboxyl group is the most frequently employed nucleophilic (in deprotonated form) and electrophilic (in protonated form) agent involved in activation of molecules by the mechanism of general base and acidic catalyses in the catalytic sites of enzymes. Glycine is a unique amino acid possessing the highest possibilities for rotation along C-C and C-N bonds of the polypeptide chain. The conservative fixation of the glycine residue in polypeptide chains of related enzymes provides a possibility for directed assembly of amino acid residues into the catalytic subsite structure. It is possible that the conservative glycines provide known conformational mobility of the protein and the active site. Methods of molecular modeling were used for analysis of structural substitutions of conservative and non-conservative glycines and their effects on geometry of catalytic site of typical hydrolases. The substitution of glycine(s) for alanine significantly altered the catalytic site structures.

Binding Sites↗

PubMed2002

Influence of anthropogenic aerosol on cloud optical depth and albedo shown by satellite measurements and chemical transport modeling.

The Twomey effect of enhanced cloud droplet concentration, optical depth, and albedo caused by anthropogenic aerosols is thought to contribute substantially to radiative forcing of climate change over the industrial period. However, present model-based estimates of this indirect forcing are highly uncertain. Satellite-based measurements would provide global or near-global coverage of this effect, but previous efforts to identify and quantify enhancement of cloud albedo caused by anthropogenic aerosols in satellite observations have been limited, largely because of strong dependence of albedo on cloud liquid water path (LWP), which is inherently highly variable. Here we examine satellite-derived cloud radiative properties over two 1-week episodes for which a chemical transport and transformation model indicates substantial influx of sulfate aerosol from industrial regions of Europe or North America to remote areas of the North Atlantic. Despite absence of discernible dependence of optical depth or albedo on modeled sulfate loading, examination of the dependence of these quantities on LWP readily permits detection and quantification of increases correlated with sulfate loading, which are otherwise masked by variability of LWP, demonstrating brightening of clouds because of the Twomey effect on a synoptic scale. Median cloud-top spherical albedo was enhanced over these episodes, relative to the unperturbed base case for the same LWP distribution, by 0.02 to 0.15.

Aerosols↗

PubMed1996

Transforming growth factor-beta 1 inhibits regeneration of renal proximal tubular cells after oxidant exposure.

Transforming growth factor-beta (TGF-beta), a regulatory cytokine expressed in the kidney, plays a role in nephrogenic repair. This study utilized a chemical model of renal proximal tubule cellular injury and regeneration to investigate the effects of TGF-beta 1 on regeneration. Confluent monolayers of rabbit renal proximal tubular cells (RPTC) in primary culture exposed to the oxidant t-butylhydroperoxide (800 microM TBHP) for 1.5 hours were 24% confluent after 24 hours. Confluency increased to 50% 4 days after TBHP exposure. Recovery of monolayer confluency was associated with increased monolayer protein but not with DNA content. Daily treatment of injured monolayers with TGF-beta 1 inhibited the recovery of monolayer confluency and inhibited recovery of protein content in a concentration-dependent manner (0.02-1 ng/mL). DNA content of injured monolayers was not altered by TGF-beta 1. A single treatment of injured monolayers with 0.2 ng/mL (8 pM) TGF-beta 1 inhibited recovery of monolayer confluency and protein content without altering monolayer DNA content. These data show that a single 24 hour exposure to a low concentration (8 pM) of TGF-beta 1 inhibits regeneration of renal proximal tubule cell monolayers following oxidative injury by inhibiting, in part, cellular migration/spreading.

Animals↗

PubMed2006

FlexNovo: structure-based searching in large fragment spaces.

We present a new molecular design program, FlexNovo, for structure-based searching within large fragment spaces following a sequential growth strategy. The fragment spaces consist of several thousands of chemical fragments and a corresponding set of rules that specify how the fragments can be connected. FlexNovo is based on the FlexX molecular docking software and makes use of its incremental construction algorithm and the underlying chemical models. Interaction energies are calculated by using standard scoring functions. Several placement geometry, physicochemical property (drug-likeness), and diversity filter criteria are directly integrated into the "build-up" process. FlexNovo has been used to design potential inhibitors for four targets of pharmaceutical interest (dihydrofolate reductase, cyclin-dependant kinase 2, cyclooxygenase-2, and the estrogen receptor). We have carried out calculations using different diversity parameters for each of these targets and generated solution sets containing up to 50 molecules. The compounds obtained show that FlexNovo is able to generate a diverse set of reasonable molecules with drug-like properties. The results, including an automated similarity analysis with the Feature Tree program, indicate that FlexNovo often reproduces structural motifs as well as the corresponding binding modes seen in known active structures.

Cyclin-Dependent Kinase 2↗

PubMed2001

Brief history of glyoxalase I and what we have learned about metal ion-dependent, enzyme-catalyzed isomerizations.

Glyoxalase I, a member of the metalloglutathione (GSH) transferase superfamily, plays a critical detoxification role in cells by catalyzing the conversion of cytotoxic methylglyoxal (as the diastereomeric GSH-thiohemiacetals) to S-D-lactoylglutathione via a 1,2-hydrogen transfer. The mechanism-of-action of this Zn2+-metalloenzyme has been the subject of considerable controversy over the past 50 years. Key issues relate to the role of the active-site metal ion in catalysis and how the enzyme is able to use directly both diastereomeric thiohemiacetals as substrates. The results of recent X-ray crystallographic measurements on the enzyme in complex with a transition state analogue and site-directed mutagenesis studies now strongly support a base-mediated, proton-transfer mechanism in which the bound diastereomeric substrates undergo catalytic interconversion before the 1S-diastereomer goes to product via a Zn2+-coordinated, cis-enediolate intermediate. Comparisons with chemical model systems suggest that Zn2+-coordination of thiohemiacetal substrate will dramatically increase the thermodynamic and kinetic acidity of the C1-H bond of substrate. In the human enzyme, the carboxyl group of Glu (172) is well positioned to catalyze a suprafacial proton transfer between the adjacent carbons of substrate. The Zn2+-coordinated carboxyl group of Glu(99) is a reasonable candidate to catalyze proton transfer between the Zn2+-coordinated oxygen atoms of the enediolate intermediate. Other Zn2+ metalloenzymes appear to use similar reaction mechanisms to facilitate proton transfers.

Catalytic Domain↗

PubMed1991

Upper limits for the ethyl-cyanide abundances in TMC-1 and L134N: chemical implications.

We have sought interstellar ethyl-cyanide via its 2(02)-1(01) transition towards two cold, dark clouds and report upper limits of the total column densities of 3 x 10(12) cm-2 and 2 x 10(12) cm-2 for TMC-1 and L134N, respectively. We also observed the 2(02)-1(01) transition of vinyl cyanide previously identified in TMC-1 by Matthews and Sears (1983b). The detection of vinyl cyanide and the non-detection of ethyl cyanide in TMC-1 are consistent with gas phase ion-molecule chemical models, and there is thus no necessity of invoking grain surface synthesis for vinyl cyanide in cold clouds.

Acrylonitrile↗

PubMed1996

Ablation and chemistry of meteoric materials in the atmosphere of Titan.

We compute the input of meteoric materials expected on Titan, and integrate this dust model with an ablation model and a comprehensive chemical model, investigating the effects on the atmosphere and surface. We find that a water deposition of approximately 10-100 times the expected interplanetary dust flux, or a recent large impact, is required to produce the observed CO2 abundance. Ionisation due to meteoric activity is not likely to be higher than that due to other sources.

Atmosphere↗

PubMed1981

Growth of a hypercycle and comparison with conventional autocatalysis.

The hypercycle is a chemical model for reproduction which has been advocated for early stages of biological evolution. Its advantage is thought to lie in the high rate of growth conferred by hyperbolic kinetics. Earlier work has also indicated a saturation phase at large constituent concentrations. The present paper shows that both the saturation phase and the phase of hyperbolic growth have been introduced into the kinetics by making some of the reactions reversible. Reversibility is not essential to the operation of the hypercycle and the system with irreversible reactions grows faster. However, even the fastest hypercycle does not grow as fast as the simple autocatalyst obtained by removing that reaction which is characteristic of the hypercycle. Also, both because the hypercycle is not a coherent system and because its growth requires reactions among separated constituents in the medium, it is more subject to decay than a simple autocatalytic particle. With greater complexity, slower growth, and more severe decay, the hypercycle is not a satisfactory alternative to conventional models of reproduction.

Catalysis↗

PubMed2006

UV/vis, 1H, and 13C NMR spectroscopic studies to determine mangiferin pKa values.

The acid constants of mangiferin (a natural xanthonoid) in aqueous solution were determined through an UV/vis spectroscopic study employing the SQUAD program as a computational tool. A NMR study complements the pK(a) values assignment and evidences a H-bridge presence on 1-C. The chemical model used was consistent with the experimental data obtained. The pK(a) values determined with this procedure were as follows: H(4)(MGF)=H(3)(MGF)(-)+H(+), pKa1 (6-H)=6.52+/-0.06; H(3)(MGF)(-)=H(2)(MGF)(2-)+H(+), pKa2 (3-H)=7.97+/-0.06; H(2)(MGF)(2-)=H(MGF)(3-)+H(+), pKa3 (7-H)=9.44+/-0.04; H(MGF)(3-)=(MGF)(4-)+H(+), pKa4 (1-H)=12.10+/-0.01; where it has been considered mangiferin C(19)H(18)O(11) as H(4)(MGF). Mangiferin UV/vis spectral behavior, stability study in aqueous solution as well as NMR spectroscopy studies: one-dimensional (1)H,(13)C, 2D correlated (1)H/(13)C performed by (g)-HSQC and (g)-HMBC methods; are also presented. pK(a) values determination of H(4)(MGF) in aqueous solution is a necessary contribution to subsequent pharmacokinetic study, and a step towards the understanding of its biological effects.

Carbon Isotopes↗

PubMed1999

Methane emission from lakes.

A physico-chemical model to describe methane and carbon dioxide emission from lakes was developed. The model describes the emission by diffusion, bubbles and plants. The intensity of the fluxes can be calculated either for total or particular emission in dependence on gas bubbles composition. It was found, that diffusional (Q) and bubble (J) fluxes depend on the methane molar ratio (X) in bubbles as follows: [formula: see text]. The model allows to estimate the role of the methane oxidation by atmospheric oxygen in the total methane flux. It was shown, that the methane oxidation does not influence much methane fluxes to the atmosphere for most of the experimentally observed situations.

Algorithms↗

PubMedDate not supplied

Multicomponent evaluations of the oxidising actions and status of a peroxoborate-containing tooth-whitening system in whole human saliva using high resolution proton NMR spectroscopy.

High resolution 1H nuclear magnetic resonance (NMR) spectroscopy was employed to conduct a multicomponent investigation of the oxidation of salivary biomolecules by peroxoborate present in a tooth-whitening dentifrice formulation. The results acquired demonstrated that peroxoborate gave rise to the oxidative decarboxylation of the hydrogen peroxide scavenger pyruvate, a reaction generating acetate and CO2 as products. Experiments performed on chemical model systems confirmed the oxidative consumption of pyruvate by dentifrice-derived peroxoborate, and also revealed that the salivary electron donors cysteine and methionine (precursors to volatile sulphur compounds), were oxidised to cystine and methionine sulphoxide respectively. The biochemical and periodontal significance of these results is discussed.

Borates↗

PubMed2003

Ultraviolet spectrophotometric characterization of copper(II) complexes with imidazole N-methyl derivatives of L-histidine in aqueous solution.

In this study we considered pi-methyl-L-histidine (pi-methis) and tau-methyl-L-histidine (tau-methis) as ligands for copper(II) ion, in order to clarify, by means of ultraviolet (UV) spectroscopy in aqueous solution (T = 25 degrees C, I = 0.1 M), some aspects of the co-ordination mode with respect to other ligands of a previous study in which copper(II) complexes of L-histidine, N-acetyl-L-histidine, histamine, L-histidine methyl ester or carnosine were investigated. Particularly, UV spectra (300-400 nm) were recorded on solutions at various pH values, containing each binary system Cu-L; afterwards, an UV absorption spectrum for single complexes was calculated, taking into account the chemical model previously assessed, in order to fulfil a correct spectrum-structure correlation. The problem related to the eventual superimposition of the CT shoulder (approximately 330 nm) to copper(II) of OH- and imidazole pyridine nitrogen groups were now solved by means of a comparison of the UV spectra of dimer species formed by both pi-methis or tau-methis. Finally, copper(II) complex formation with 2,2'-bipyridine was taken into account to compare the behaviour of pyridine (from 2,2'-bipyridine) and pyridine imidazole nitrogens (from pi-methis or tau-methis) with respect to the UV charge transfer process to copper(II) ion.

Copper↗

PubMed2003

Cooperative biosorption of copper on calcium alginate enclosing iminodiacetic type resin.

Composite gels of calcium alginate containing iminodiacetic type resin were prepared as a chemical analogue of biological tissues and membrane such as the cell wall. This chemical model was applied in copper biosorption from synthetic aqueous solutions. Experimental data on the composite were compared to those obtained for the biopolymer and the iminodiacetic-type resin separately and fitted into the ion exchange equilibrium model proposed in this work, which basically assumes that metal retention is the sum of the metal loaded onto the biopolymer and onto the resin. This model is tested with experimental data on copper biosorption on composite gels, including the equilibrium expressions of all the ionic species that are present in the system, the fraction of metal enclosed in the gel fluid, the gel volume variation, and the Donnan equilibrium theory. Another simplified model that only requires one equilibrium constant for each metal in the resin is shown to fit the results of the experiment fairly well, but it proves necessary to include an empirical parameter n into the equilibrium equation of copper in the resin to obtain the best fit of experimental data.

Adsorption↗

PubMed2003

Binding of mercury(II) to aquatic humic substances: influence of pH and source of humic substances.

Conditional distribution coefficients (K(DOM')) for Hg(II) binding to seven dissolved organic matter (DOM) isolates were measured at environmentally relevant ratios of Hg(II) to DOM. The results show that K(DOM') values for different types of samples (humic acids, fulvic acids, hydrophobic acids) isolated from diverse aquatic environments were all within 1 order of magnitude (10(22.5 +/-1.0)-10(23.5 +/- 1.0)) L kg(-1)), suggesting similar Hg(ll) binding environments, presumably involving thiol groups, for the different isolates. K(DOM') values decreased at low pHs (4) compared to values at pH 7, indicating proton competition for the strong Hg(II) binding sites. Chemical modeling of Hg(II)-DOM binding at different pH values was consistent with bidentate binding of Hg(II) by one thiol group (pK(a) = 10.3) and one other group (pK(a) = 6.3) in the DOM, which is in agreement with recent results on the structure of Hg(II)-DOM bonds obtained by extended X-ray absorption fine structure spectroscopy (EXAFS).

Environmental Monitoring↗

PubMed2004

Antimony(III) binding to humic substances: influence of pH and type of humic acid.

Conditional distribution coefficients (Dom) for Sb(III) binding to three commercial humic acids (terrestrial, coal, and aquatic) were measured at environmentally relevant Sb(III)/DOC ratios and as a function of pH using an equilibrium dialysis method. Maximum binding of Sb(III) was observed around pH 6 for two of the humic acids. The third humic acid showed constant Dom values up to pH 6 and decreasing Dom values for pH > 6. Sb(III)/DOC ratio was found to be important for Dom (20 times higher Dom for 60 times lower Sb(III)/DOC ratio). Moreover, Dom depends on the individual humic acid, suggesting that different functional groups are involved and/or different degrees of stabilization by chelation or H-bridges. Chemical modeling of Sb(III)-humics binding at different pH values is consistent with two binding sites involving (i) a phenolic entity forming a neutral complex and (ii) a carboxylic entity forming a negatively charged complex. Under environmentally relevant conditions, over 30% of total Sb(III) may be bound to natural organic matter.

Adsorption↗

PubMed2005

Methyl transfer in glycine N-methyltransferase. A theoretical study.

Density functional theory calculations using the hybrid functional B3LYP have been performed to study the methyl transfer step in glycine N-methyltransferase (GNMT). This enzyme catalyzes the S-adenosyl-L-methionine (SAM)-dependent methylation of glycine to form sarcosine. The starting point for the calculations is the recent X-ray crystal structure of GNMT complexed with SAM and acetate. Several quantum chemical models with different sizes, employing up to 98 atoms, were used. The calculations demonstrate that the suggested mechanism, where the methyl group is transferred in a single S(N)2 step, is thermodynamically plausible. By adding or eliminating various groups at the active site, it was furthermore demonstrated that hydrogen bonds to the amino group of the glycine substrate lower the reaction barrier, while hydrogen bonds to the carboxylate group raise the barrier.

Computer Simulation↗

PubMed2006

Theoretical study of the methyl transfer in guanidinoacetate methyltransferase.

The reaction mechanism of the guanidinoacetate methyltransferase (GAMT) enzyme has been investigated by means of density functional theory using the B3LYP hybrid functional. GAMT catalyzes the S-adenosyl-L-methionine (SAM)-dependent methylation of guanidinoacetate (GAA) to form creatine. A quantum chemical model was built on the basis of the recent crystal structure of GAMT complexed with S-adenosylhomocysteine (SAH) and GAA. The methyl group transfer from SAM to N(E) of GAA is shown to occur concertedly with a proton transfer from NE to the neighboring OD1 of Asp134. Good agreement is found between the calculated barrier and the experimental rate.

Catalysis↗

PubMedDate not supplied

Peroxyl radical oxidation of beta-carotene: formation of beta-carotene epoxides.

A chemical model system was used to study peroxyl radical trapping reactions of beta-carotene (1) that may contribute to its antioxidant action in biological systems. Peroxyl radicals generated in hexane by thermolysis of azobis(2,4-dimethylvaleronitrile) (AMVN) at 37 degrees C oxidized 1 to 5,6-epoxy-beta,beta-carotene (2) and a previously unreported product, 15,15'-epoxy-beta,beta-carotene (6), in addition to several unidentified polar products. The epoxide products were purified by high-performance liquid chromatography and characterized by UV-vis spectroscopy, mass spectrometry, and 1H NMR. Epoxides 2 and 6 and the polar products were formed together from the initial stages of the reaction. As the reaction progressed, the epoxides were oxidized further to more polar products. Although epoxides 2 and 6 were formed at similar rates, 2 was oxidized more rapidly than 6. Incubations with [14C]-1 indicate that at their maximum concentrations 2 and 6 account for approximately 20% of the radiolabeled oxidation products. Epoxide formation may result from peroxyl radical addition to the polyene chain to form a resonance-stabilized peroxyl radical adduct. Peroxide bond scission would yield the epoxide and release an alkoxyl radical. Although this two-step sequence produces no net radical trapping, it could produce a kinetically significant inhibition of peroxyl radical propagation and account, in part, for the antioxidant properties of 1. Epoxides 2 and 6 are structurally distinct from retinoids, which are the metabolic products of 1, and therefore may be useful biochemical markers for its antioxidant actions.

Azo Compounds↗