Computational Insights into β-Carboline Inhibition of Monoamine Oxidase A

Monoamine oxidases (MAOs) are an important group of enzymes involved in the degradation of neurotransmitters and their imbalanced mode of action may lead to the development of various neuropsychiatric or neurodegenerative disorders. In this work, we report the results of an in-depth computational study in which we performed a static and a dynamic analysis of a series of substituted β-carboline natural products, found mainly in roasted coffee and tobacco smoke, that bind to the active site of the MAO-A isoform. By applying molecular docking in conjunction with structure-based pharmacophores and molecular dynamics simulations coupled with dynamic pharmacophores, we extensively investigated the geometric aspects of MAO-A binding. To gain insight into the energetics of binding, we used the linear interaction energy (LIE) method and determined the key anchors that allow productive β-carboline binding to MAO-A. The results presented herein could be applied in the rational structure-based design and optimization of β-carbolines towards preclinical candidates that would target the MAO-A enzyme and would be applicable especially in the treatment of mental disorders such as depression.     

New angle‐dependent potential energy function for backbone–backbone hydrogen bond in protein–protein interactions

Backbone–backbone hydrogen bonds (BBHBs) are one of the most abundant interactions at the interface of protein–protein complex. Here, we propose an angle‐dependent potential energy function for BBHB based on density functional theory (DFT) calculations and the operation of a genetic algorithm to find the optimal parameters in the potential energy function. The angular part of the energy funtion is assumed to be the product of the power series of sine and cosine functions with respect to the two angles associated with BBHB. Two radial functions are taken into account in this study: Morse and Leonard‐Jones 12‐10 potential functions. Of these two functions under consideration, the former is found to be more accurate than the latter in terms of predicting the binding energies obtained from DFT calculations. The new HB potential function also compares well with the knowledge‐based potential derived by applying Boltzmann statistics for a variety of protein–protein complexes in protein data bank. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

Preparation of a novel carboxyl stationary phase by “thiol‐ene” click chemistry for hydrophilic interaction chromatography

A novel carboxyl‐bonded silica stationary phase was prepared by “thiol‐ene” click chemistry. The resultant Thiol‐Click‐COOH phase was evaluated under hydrophilic interaction liquid chromatography (HILIC) mobile phase conditions. A comparison of the chromatographic performance of Thiol‐Click‐COOH and pure silica columns was performed according to the retention behaviors of analytes and the charged state of the stationary phases. The results indicated that the newly developed Thiol‐Click‐COOH column has a higher surface charge and stronger hydrophilicity than the pure silica column. Furthermore, the chromatographic behaviors of five nucleosides on the Thiol‐Click‐COOH phase were investigated in detail. Finally, a good separation of 13 nucleosides and bases, and four water‐soluble vitamins was achieved.     

One Singularly Perturbed Problem of Turbulent Gas Dynamics

The problem of the interaction of a Prandtl–Mayer wave with a shear layer is solved using the small parameter method for the case where the flow vorticity in the shear layer is small. A direct expansion is constructed and its inadequacy at large distances from the vortex layer is proved. The strained coordinate method is used to obtain a uniformly adequate expansion. It is shown that for certain velocity distributions in the shear layer, the characteristics in the reflected simple wave resulting from the interaction intersect each other and a shock arises in the flow. There coordinates of the shock origin and the function describing the shock shape are obtained.     

气相色谱法研究聚辛烯-1与不同溶剂的热力学相互作用

用气相色谱法测定了聚辛烯－１与８种溶剂的Ｆｌｏｒｙ－Ｈｕｇｇｉｎｓ相互作用参数χ１和聚辛烯－１的溶解度参数,确定了χ１与温度的数学关系式。测定结果表明聚辛烯－１溶于正辛烷是一个放热过程。     

A computational study of the chromatographic separation of racemic mixtures

Summary A model is devised using molecular mechanics to simulate chromatographic separations of enantiomers. Theoretical results derived from this model are compared with experimental findings obtained using supercritical fluid chromatography. The model is then developed to incorporate the effects of binding the stationary phase to a matrix. Computed results show that addition of the matrix into the model has significant effects on the ability of the stationary phase to separate racemic mixtures.     

Hydrolysis of (CH3)3Sn+ in Various Salt Media

The hydrolysis of trimethyltin(IV) has been studied by potentiometry (H⁺ -glass electrode) and calorimetry in various salt media (NaNO₃, NaCl, KCl, Na₂SO₄, and NaNO₃—NaCl mixtures). The effect of ionic strength on the hydrolysis constants is accounted for by a simple Debye–Hückel type equation and by Pitzer equations. The results allow us to obtain H for hydrolysis and the temperature dependence of the Pitzer parameters. The resulting coefficients can be used to examine the speciation of (CH₃)₃Sn⁺ in multicomponent electrolyte solutions, such as natural waters, over a wide range of temperature and ionic strength.     

Pseudopotential study of the ground and excited states of Yb2

The ground state of the van der Waals-type lanthanide dimer Yb₂ has been studied by means of relativistic energy-consistent ab initio pseudopotentials using three different core definitions. Electron correlation was treated by coupled-cluster theory, whereby core-valence correlation effects have been accounted for either explicitly by correlating the energetically highest coreorbitals or implicitly by means of an effective core-polarization potential. Results for the first and second atomic ionization potentials, the atomic dipole polarizability, and the spectroscopic constants of the molecular ground state are reported. Low-lying excited states have been investigated with spin-orbit configuration interaction calculations. It is also demonstrated for the whole lanthanide series that correlation effects due to the atomic-like, possibly open 4f-shell in lanthanides can be modeled effectively by adding a core-polarization potential to pseudopotentials attributing the 4f-shell to the core. Received: 3 April 1998 / Accepted: 27 July 1998 / Published online: 9 October 1998