Two-dimensional NMR lineshape analysis

NMR titration experiments are a rich source of structural, mechanistic, thermodynamic and kinetic information on biomolecular interactions, which can be extracted through the quantitative analysis of resonance lineshapes. However, applications of such analyses are frequently limited by peak overlap inherent to complex biomolecular systems. Moreover, systematic errors may arise due to the analysis of two-dimensional data using theoretical frameworks developed for one-dimensional experiments. Here we introduce a more accurate and convenient method for the analysis of such data, based on the direct quantum mechanical simulation and fitting of entire two-dimensional experiments, which we implement in a new software tool, TITAN (TITration ANalysis). We expect the approach, which we demonstrate for a variety of protein-protein and protein-ligand interactions, to be particularly useful in providing information on multi-step or multi-component interactions

Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design

Optimization of patients with arterial hypertension in railway workers on the example of large industrial city

Trains to Russia is a state- industry. By a steady process of integration of Russia into the world economy, the Russian railways are actively involved in the global transportation system. In 2010, the size of the transit of goods increased by 3 times compared to 2005. Today, despite the constant, systematic work on health and the prevention of violations of workers' health in Russia has been the intensification of stress at work, does not decrease the number of occupational diseases and a widening range of production related diseases. Russian railway transport held constant purposeful work on occupational safety and health and working conditions of workers industry, which is currently being-carried out within the branch program1 Work safety in rail transportArterial hypertension (AH) is one of the most common diseases, the occurrence of which is associated with a significantly increased risk of cardiovascular morbidity and mortality.Железнодорожный транспорт для России является государствообразующей отраслью. На фоне неуклонного процесса интеграции России с мировой экономикой, российские железные дороги активно включаются в мировую транспортную систему. В 2010 году размер транзитных перевозок грузов возрос в 3 раза по сравнению с 2005 годом. Сегодня, несмотря на постоянную, планомерную работу по охране труда и профилактике нарушений здоровья трудящихся, в России отмечается усиление интенсивности стресса на производстве, не уменьшается число профессиональных болезней и все более расширяется спектр производственно зависимых заболеваний. На железнодорожном транс­ порте России проводится постоянная целенаправленная работа по охране труда и улучшению условий трудящихся отрасли, которая в настоящее время осуществляется в рамках отраслевой программы «Безопасность труда на железнодорожном транспорте». Артериальная гипертония (АГ) является одним из самых распространенных заболеваний, возникновение которого связано со значительным увеличением риска развития сердечно-сосудистых осложнений и смертности. В жизни человека трудовые процессы играют огромную роль, поэтому следует знать, как работа влияет на сердечно-сосудистую систему, в частности на заболеваемость гипертонической болезнью. Достаточно часто повышенное артериальное давление отмечается у лиц, профессии которых связаны с частыми нервно-психическими стрессами (например, у административных и научных работников, шоферов, рабочих со сдельной оплатой труда и т.д.). В настоящее время имеются редкие исследования, посвященные изучению состояния сердечно-сосудистой системы при влиянии производственных вредностей, изучению системного управления профессиональным риском и оценки уровня здоровья, степени приверженности лечению у работников такой сложной сферы, которой является железнодорожный транспорт