排序方式: 共有177条查询结果,搜索用时 15 毫秒
171.
Michielan L Bacilieri M Schiesaro A Bolcato C Pastorin G Spalluto G Cacciari B Klotz KN Kaseda C Moro S 《Journal of chemical information and modeling》2008,48(2):350-363
The integration of ligand- and structure-based strategies might sensitively increase the success of drug discovery process. We have recently described the application of Molecular Electrostatic Potential autocorrelated vectors (autoMEPs) in generating both linear (Partial Least-Square, PLS) and nonlinear (Response Surface Analysis, RSA) 3D-QSAR models to quantitatively predict the binding affinity of human adenosine A3 receptor antagonists. Moreover, we have also reported a novel GPCR modeling approach, called Ligand-Based Homology Modeling (LBHM), as a tool to simulate the conformational changes of the receptor induced by ligand binding. In the present study, the application of both linear and nonlinear 3D-QSAR methods and LBHM computational techniques has been used to depict the hypothetical antagonist binding site of the human adenosine A2A receptor. In particular, a collection of 127 known human A2A antagonists has been utilized to derive two 3D-QSAR models (autoMEPs/PLS&RSA). In parallel, using a rhodopsin-driven homology modeling approach, we have built a model of the human adenosine A2A receptor. Finally, 3D-QSAR and LBHM strategies have been utilized to predict the binding affinity of five new human A2A pyrazolo-triazolo-pyrimidine antagonists finding a good agreement between the theoretical and the experimental predictions. 相似文献
172.
Tasinato N Regini G Stoppa P Pietropolli Charmet A Gambi A 《The Journal of chemical physics》2012,136(21):214302
Difluoromethane (CH(2)F(2), HFC-32) is a molecule used in refrigerant mixtures as a replacement of the more environmentally hazardous, ozone depleting, chlorofluorocarbons. On the other hand, presenting strong vibration-rotation bands in the 9 μm atmospheric window, it is a greenhouse gas which contributes to global warming. In the present work, the vibrational and ro-vibrational properties of CH(2)F(2), providing basic data for its atmospheric modeling, are studied in detail by coupling medium resolution Fourier transform infrared spectroscopy to high-level electronic structure ab initio calculations. Experimentally a full quantum assignment and accurate integrated absorption cross sections are obtained up to 5000 cm(-1). Ab initio calculations are carried out by using CCSD(T) theory and large basis sets of either the correlation consistent or atomic natural orbital hierarchies. By using vibrational perturbation theory to second order a complete set of vibrational and ro-vibrational parameters is derived from the ab initio quartic anharmonic force fields, which well compares with the spectroscopic constants retrieved experimentally. An excellent agreement between theory and experiment is achieved for vibrational energy levels and integrated absorption cross sections: transition frequencies up to four quanta of vibrational excitation are reproduced with a root mean square deviation (RMSD) of 7 cm(-1) while intensities are predicted within few km mol(-1) from the experiment. Basis set performances and core correlation effects are discussed throughout the paper. Particular attention is focused in the understanding of the anharmonic couplings which rule the vibrational dynamics of the |ν(1)>, |2ν(8)>, |2ν(2)> three levels interacting system. The reliability of the potential energy and dipole moment surfaces in reproducing the vibrational eigenvalues and intensities as well as in modeling the vibrational and ro-vibrational mixings over the whole 400-5000 cm(-1) region is also demonstrated by spectacular spectral simulations carried out by using the ro-vibrational Hamiltonian constants, and the relevant coupling terms, obtained from the perturbation treatment of the ab initio anharmonic force field. The present results suggest CH(2)F(2) as a prototype molecule to test ab initio calculations and theoretical models. 相似文献
173.
174.
The reaction of dihydrolipoic acid (DHLA) with 5-hydroxy-1,4-naphthoquinone (juglone) gives rise to the novel naphtho[1,4]dithiepine derivatives through ring expansion of an unstable spirocyclic 1,3-dithiane intermediate, which was isolated and completely characterized. Reported herein is also the characterization of novel reaction products of DHLA with other naphthoquinones and the extension of the study to the spirocyclic adduct formed by reaction with a representative 2-substituted naphthoquinone. 相似文献
175.
The inception of the emission trading scheme in Europe has contributed to power price increases. Energy intensive industries
have reacted by arguing that this may affect their competitiveness and will induce them to leave Europe. Taking up a proposal
of these industrial sectors, we explore the possible application of special contracts, where electricity is sold at average
generation cost to mitigate the impact of CO2 cost on power prices. The model supposes fixed generation capacities. We first consider a reference model representing a
perfectly competitive market where all consumers (industries and the rest of the market) are price-takers and buy electricity
at short-run marginal cost. We then change the market design by assuming that energy intensive industries pay power either
at a regional or at a zonal average cost price. The analysis is conducted with simulation models applied to the Central Western
European power market. The models are implemented in GAMS/PATH.
This work has been financially supported by the Chair Lhoist Berghmans in Environmental Economics and Management and by the
Italian project PRIN 2006, Generalized monotonicity: models and applications, whose national responsible is Prof. Elisabetta
Allevi. 相似文献
176.
Giorgia Bellomonte Camillo Trapani Salvatore Triolo 《Rendiconti del Circolo Matematico di Palermo》2009,58(2):265-274
The relationship between the notion of closedness, lower semicontinuity and completeness (of a quotient) of the domain of
a positive sesquilinear form defined on a subspace of a topological vector space is investigated and sufficient conditions
for their equivalence are given.
相似文献
177.
Dr. Sara Cuadros Dr. Giulio Goti Giorgia Barison Alfredo Raulli Tommaso Bortolato Prof. Giorgio Pelosi Dr. Paolo Costa Prof. Luca Dell'Amico 《Angewandte Chemie (International ed. in English)》2023,62(31):e202303585
Here, we report a general approach to the synthesis of the difluoroalkyl bicycloalkanes (CF2-BCAs), as structural surrogates of aryl ketones and ethers. The chemistry is driven by a dihydrobenzoacridine photocatalyst, that engages in a catalytic electron-donor acceptor (EDA) complex, or directly reduces the fluorinated substrate. These two convergent manifolds lead to the generation of the R-CF2 radical, that reacts with the [1.1.1]- or [3.1.1.]-propellane. The method is extremely general, and extendable to complex bioactive molecules (30 examples, up to 87 % yield). The structural features of the CF2-BCP hybrid bioisostere were investigated by single crystal X-ray. Finally, we synthesised a CF2-BCP analogue of a Leukotriene A4 hydrolase inhibitor, replacing the original aryl ether motif. In silico docking studies indicated that this new analogue maintains the same arrangement within the enzyme pocket, profiling the use of the CF2-BCA hybrid bioisostere in medicinal chemistry settings. 相似文献