Homology modeling and molecular dynamics study of Mycobacterium tuberculosis urease

Introduction. M. tuberculosis urease (MTU) is an attractive target for chemotherapeutic intervention in tuberculosis by designing new safe and efficient enzyme inhibitors. A prerequisite for designing such inhibitors is an understanding of urease's three-dimensional (3D) structure organization. 3D structure of M. tuberculosis urease is unknown. When experimental three-dimensional structure of a protein is not known, homology modeling, the most commonly used computational structure prediction method, is the technique of choice. This paper aimed to build a 3D-structure of M. tuberculosis urease by homology modeling and to study its stability by molecular dynamics simulations. Materials and methods. To build MTU model, five high-resolution X-ray structures of bacterial ureases with three-subunit composition (2KAU, 5G4H, 4UBP, 4СEU, and 4EPB) have been selected as templates. For each template five stochastic alignments were created and for each alignment, a three-dimensional model was built. Then, each model was energy minimized and the models were ranked by quality Z-score. The MTU model with highest quality estimation amongst 25 potential models was selected. To further improve structure quality the model was refined by short molecular dynamics simulation that resulted in 20 snapshots which were rated according to their energy and the quality Z-score. The best scoring model having minimum energy was chosen as a final homology model of 3D structure for M. tuberculosis. The final model of MTU was also validated by using PDBsum and QMEAN servers. These checks confirmed good quality of MTU homology model. Results and discussion. Homology model of MTU is a nonamer (homotrimer of heterotrimers, (αβγ)3) consisting of 2349 residues. In MTU heterotrimer, sub-units α, β, and γ tightly interact with each other at a surface of approximately 3000 Å2. Sub-unit α contains the enzyme active site with two Ni atoms coordinated by amino acid residues His347, His349, carbamylated Lys430*, His459, His485, Asp 573, Gly490. Helix-turn-helix motif (residues 524-545) forms a mobile flap that covers the active site and is in closed conformation impeding access to the enzyme active site. The structural stability of MTU model was checked by molecular dynamics simulation in explicit water at 300 К and рН 7,4. During the simulation, root mean square deviations of Сα atoms (RMSD Сα) and root mean square fluctuations (RMSF) of amino acid residues of MTU were monitored for 60 ns. Also, the distance between the loop that covers the active site and the dinickel center was monitored. Analysis of MD trajectory indicate that the enzyme global structure is stable and the flap covering the active center remains in closed state during the simulation time. Conclusion. Predicted three-dimensional structure of M. tuberculosis urease can be used in the studies of structure-function relationships of the enzyme, in designing new safe and efficient enzyme inhibitors aimed to struggle with infectious diseases promoted by urease activity

Forward observables at RHIC, the Tevatron run II and the LHC

We present predictions on the total cross sections and on the ratio of the real part to the imaginary part of the elastic amplitude (rho parameter) for present and future pp and pbar p colliders, and on total cross sections for gamma p -> hadrons at cosmic-ray energies and for gamma gamma -> hadrons up to sqrt(s)=1 TeV. These predictions are based on a study of many possible analytic parametrisations and invoke the current hadronic dataset at t=0. The uncertainties on total cross sections, including the systematic theoretical errors, reach 1% at RHIC, 3% at the Tevatron, and 10% at the LHC, whereas those on the rho parameter are respectively 10%, 17%, and 26%.Comment: 11 pages, 2 figures, LaTeX, presented at the Second International "Cetraro" Workshop & NATO Advanced Research Workshop "Diffraction 2002", Alushta, Crimea, Ukraine, August 31 - September 6, 200

МАТЕМАТИЧНЕ МОДЕЛЮВАННЯ АДСОРБЦІЙНОГО ЗАБРУДНЕННЯ В ЗАВАНТАЖЕННІ ЗНЕЗАЛІЗНЮВАЛЬНИХ ФІЛЬТРІВ

In the article the scheme of immobilization and transformation of iron forms is presented for underground water deferrization. The clarification block of the general model of physico-chemical deferrization of water is presented, taking into account the nonlinear effects of mass exchange. Separately the block of nonlinear problem of adsorption and transformation of iron oxide is considered. Using the method of dynamic averaging of the desired characteristic, approximate solutions are obtained. Executed the quantitativeanalysis of changes of the relative concentrations of free and adsorbed ferrous iron and the discrepancy between the corresponding exact and approximate solutions is estimated. The accumulation of adsorbed iron in the download is calculated.В статье приведена схема иммобилизации и трансформации форм железа при обезжелезивании подземных вод. Представлен осветительный блок общей модели физико-химического обезжелезивания воды с учетом нелинейных эффектов массообмена. Отдельно рассмотрен блок нелинейной задачи адсорбции и трансформации закиси железа. Используя метод динамического осреднения искомой характеристики, полученные приближенные ее решения.Проведен количественный анализ изменений относительных концентраций свободного и адсорбированного двухвалентного железа и оценено расхождение между соответствующими точными и приближенными решениями. Рассчитано накопления адсорбированного железа в загрузке.В статті наведено схему іммобілізації та трансформації форм заліза при знезалізненні підземних вод. Представлено освітлювальний блок загальної моделі фізико-хімічного знезалізнення води з врахуванням нелінійних ефектів масообміну. Окремо розглянутий блок нелінійної задачі адсорбції і трансформації закису заліза. Використовуючи метод динамічного осереднення шуканої характеристики, отримані наближені її розв’язки. Проведений кількісний аналіз змін відносних концентрацій вільного і адсорбованого двовалентного заліза та оцінена розбіжність між відповідними точними та наближеними розв’язками. Розраховано накопичення адсорбованого заліза в завантаженні

Thymosin β4 as basis for creation of a reparation preparation of new generation

On the basis of its multipurpose activities during regeneration of fabrics in various experiments on animals, Thymosin β4 has the potential for new researches, in kidneys and a liver, and also recovery of a spinal cord, bones and injury of ligaments. Besides, it can be useful in case of treatment of a wide range of other diseases, including concerning consequences of old bacterial damages and viral infection

Lamellar multilayer gratings with very high diffraction efficiency

The authors report here the development of a hard x-ray multilayer grating that has achieved an absolute efficiency of 34% at a wavelength of 1.54{angstrom}. The W-C multilayer itself has a reflectivity of 57% and the grating has a 0th order absolute efficiency of 36%. The origin of this extraordinarily high efficiency is that the short period and highly asymmetric structure of the gratings combined with its deep grooves allows light to interact with a large number of layer pairs. This increases angular separation of the diffraction orders and reduces the multilayer bandwidth to the point where there is little or no order to order overlap in the grating structure, and hence maximum intensity can be diffracted into a selected order. This paper reports on the development of an optimized multilayer grating and some of its unique characteristics

Competing ideologies of Russia's civil society

Many analysts and public opinion makers in the West conflate the notions of Russia’s non-systemic liberal opposition and the country’s civil society. Indeed, despite garnering the support of a minority of Russia’s population, non-systemic liberal opposition represents a well-organized civic group with a clearly articulated agenda and the ability to take action. Yet, does Russia’s civil society end there? A closer look at the country’s politics shows that Russia has a substantial conservative-traditionalist faction that has also developed agenda for action and formulated opinions. This group is anti-liberal rather than illiberal ideologically and pro-strong state/pro a geopolitically independent Russia rather than pro-Kremlin politically. The interaction between liberal and conservative civic groups represents the battle of meanings, ideas, and ethics, and ultimately determines the future trajectory of Russia’s evolution. Thus, the analysis of Russia’s civil society must represent a rather more nuanced picture than a mere study of the liberal non-systemic opposition. This article will examine the complexity of Russia’s civil society scene with reference to the interplay between the liberal opposition and conservative majority factions. The paper will argue that such complexity stems from ideological value pluralism that falls far beyond the boundaries of the liberal consensus, often skewing our understanding of political practice in Russia

Benchmarks for the Forward Observables at RHIC, the Tevatron-run II and the LHC

We present predictions on the total cross sections and on the ratio of the real part to the imaginary part of the elastic amplitude (rho parameter) for present and future pp and pbar p colliders, and on total cross sections for gamma p -> hadrons at cosmic-ray energies and for gamma gamma-> hadrons up to sqrt{s}=1 TeV. These predictions are based on an extensive study of possible analytic parametrisations invoking the biggest hadronic dataset available at t=0. The uncertainties on total cross sections, including the systematic errors due to contradictory data points from FNAL, can reach 1.9% at RHIC, 3.1% at the Tevatron, and 4.8% at the LHC, whereas those on the rho parameter are respectively 5.4%, 5.2%, and 5.4%.Comment: 11 pages, 2 figures, 4 tables, RevTeX

Modelling of the rolling process of titanium alloy tube billets in laboratory conditions on a RSP 14-40 rolling mill

The development of screw rolling technology for the production of hot-deformed tubes over Ø250 mm on a SVP-500 rolling mill faces a number of challenges that influence the quality of tubes, such as: the screw trace formed on the external surface of tubes and bending of tubes that makes impossible subsequent manufacturing operations. The following experimental and laboratory research was performed to solve these problems: a number of experimental tube billets with and without mandrels were rolled to various strains on a RSP 14-40 laboratory rolling mill to obtain the best ratio of wall thickness to the external diamete

Comparison of the calculations of the stability properties of a specific stellarator equilibrium with different MHD stability codes

A particular configuration of the LHD stellarator with an unusually flat pressure profile has been chosen to be a test case for comparison of the MHD stability property predictions of different three-dimensional and averaged codes for the purpose of code comparison and validation. In particular, two relatively localized instabilities, the fastest growing modes with toroidal mode number n = 2 and n = 3 were studied using several different codes, with the good agreement that has been found providing justification for the use of any of them for equilibria of the type considered