Економічні напрями енергетичної безпеки Європейського Союзу

Interactions between proteins are orchestrated in a precise and timedependent manner, underlying cellular function. The binding affinity, defined as the strength of these interactions, is translated into physico-chemical terms in the dissociation constant (Kd), the latter being an experimental measure that determines whether an interaction will be formed in solution or not. Predicting binding affinity from structural models has been a matter of active research for more than 40 years because of its fundamental role in drug development. However, all available approaches are incapable of predicting the binding affinity of protein–protein complexes from coordinates alone. Here, we examine both theoretical and experimental limitations that complicate the derivation of structure–affinity relationships. Most work so far has concentrated on binary interactions. Systems of increased complexity are far from being understood. The main physico-chemical measure that relates to binding affinity is the buried surface area, but it does not hold for flexible complexes. For the latter, there must be a significant entropic contribution that will have to be approximated in the future. We foresee that any theoretical modelling of these interactions will have to follow an integrative approach considering the biology, chemistry and physics that underlie protein–protein recognition

NMR relaxation and internal dynamics of ubiquitin from a 0.2 mu s MD simulation

A 0.2 mu s molecular dynamics simulation of ubiquitin in water is presented, which allows us to assess both the global tumbling in solution and the internal dynamics. The latter reveals slow motions outside the classical NMR timewindow, in agreement with recent RDC and cross-correlation measurements. Analysis of back-calculated relaxation rates using the classical NMR model-free approach reproduces the amplitudes of internal motions expressed in the order parameter, while it severely underestimates the corresponding time scales present in the simulation

Співвідношення категорій природного та позитивного права: сучасні погляди та концепції

В статье проведен анализ позитивных и негативных сторон естественно-правового и позитивного правопонимания и осуществлен поиск идеальной системы, объединяющий положительные моменты обеих концепций.In the article the analysis of positive and negative sides of absolute law and positive rights understanding is conducted and the search of the ideal system, uniting the positive moments of both conceptions, is carried out

Предопухолевая патология молочных желез в различных этнических популяциях населения Крыма

Серед жіночого населення АРК виявлені популяції із украй високою захворюваністю РМЖ (армянки - 114,25); з високою захворюваністю (слов’янки - 65,21); а також з відносно низькою захворюваністю (кримські татарки - 41,99 на 100 тис. відповідного жіночого населення; р < 0,001). Порівняльний аналіз поширеності доброякісної патології в 531 пацієнтки (399 слов’янок, 69 татарок, 63 армянки) показав, що вірогідно найбільш частими захворюваннями у вірменській популяції з високою захворюваністю РМЖ є кисты молочних залоз (Р=0,033) і вузлова форма фиброзно-кистозной хвороби (Р=0,040), які, очевидно, можна відносити до предраковой патології.In Crimean woman there are populations with very high Breast Cancer incidence (Armenians - 114,25); with high incidence (Slavs - 65,21); and with lowest incidence (Tatars - 41,99 in 100 000 woman populations; р < 0,001). In 531 patients (399 Slavs, 69 Tatars, 63 Armenians) more freqwently was diagnosed Breast Cysts (Р=0,033) and Nodular Fibrocystic disease (Р=0,040) in Armenian ethnic group with very high Breast Cancer incidence. Breast Cysts and Nodular Fibrocystic disease only are precancerous diseases of the Breast

Future opportunities and trends for e-infrastructures and life sciences: Going beyond the grid to enable life science data analysis

With the increasingly rapid growth of data in life sciences we are witnessing a major transition in the way research is conducted, from hypothesis-driven studies to data-driven simulations of whole systems. Such approaches necessitate the use of large-scale computational resources and e-infrastructures, such as the European Grid Infrastructure (EGI). EGI, one of key the enablers of the digital European Research Area, is a federation of resource providers set up to deliver sustainable, integrated and secure computing services to European researchers and their international partners. Here we aim to provide the state of the art of Grid/Cloud computing in EU research as viewed from within the field of life sciences, focusing on key infrastructures and projects within the life sciences community. Rather than focusing purely on the technical aspects underlying the currently provided solutions, we outline the design aspects and key characteristics that can be identified across major research approaches. Overall, we aim to provide significant insights into the road ahead by establishing ever-strengthening connections between EGI as a whole and the life sciences community

Науково-документальна серія книг «Реабілітовані історією»: досвід та перспективи наукового дослідження (до 95-річчя з дня народження академіка НАН України П. Т. Тронька)

У статті аналізується наукова та громадсько-політична діяльність академіка НАН України П. Т. Тронька як науковця та організатора реалізації Державної програми науково-документальної серії книг «Реабілітовані історією».В статье анализируется научная и общественно-политическая деятельность академика НАН Украины П. Т. Тронько как учёного и организатора реализации Государственной программы научно-документальной серии книг «Реабилитированные историей».The author analyzed research, political and public activity of academic P. Tronko as scholar and organizer of State program of documentary series «Rehabilitated by history»

Філософія популізму як варіант сучасної філософії

We have previously reported on the functional interaction of Lipid II with human alpha-defensins, a class of antimicrobial peptides. Lipid II is an essential precursor for bacterial cell wall biosynthesis and an ideal and validated target for natural antibiotic compounds. Using a combination of structural, functional and in silico analyses, we present here the molecular basis for defensin-Lipid II binding. Based on the complex of Lipid II with Human Neutrophil peptide-1, we could identify and characterize chemically diverse low-molecular weight compounds that mimic the interactions between HNP-1 and Lipid II. Lead compound BAS00127538 was further characterized structurally and functionally; it specifically interacts with the N-acetyl muramic acid moiety and isoprenyl tail of Lipid II, targets cell wall synthesis and was protective in an in vivo model for sepsis. For the first time, we have identified and characterized low molecular weight synthetic compounds that target Lipid II with high specificity and affinity. Optimization of these compounds may allow for their development as novel, next generation therapeutic agents for the treatment of Gram-positive pathogenic infections

Deep-learning enhancement of large scale numerical simulations

Computational astrophysic

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis