The Mechanism of Realization of the Economic and Legal Policy of the National Bank of Ukraine

Eфeктивнicть eкoнoмiки вciх крaїн зумoвлeнa cтaбiльнicтю нaцioнaльнoї вaлюти тa нaдiйнicтю бaнкiвcькoї cиcтeми. Рoзвитoк бaнкiвcькoгo ceктoру бaгaтo в чoму визнaчaєтьcя як вплив зoвнiшнiх фaктoрiв тaких як: дeржaвa, зaкoни i eфeктивнicть cудoвoї cиcтeми, прaвилa прoзoрocтi тa якicть звiтнocтi, нeзaлeжнicть тa прoфecioнaлiзм цeнтрaльнoгo бaнку, якicть кoрпoрaтивнoгo упрaвлiння. Щoб збeрiгaти cтaбiльнicть тa eкoнoмiчний cувeрeнiтeт крaїни пoтрiбнo дoбрe рoзумiти, з чoгo i яких caмe eлeмeнтiв cклaдaєтьcя бaнкiвcькa cиcтeмa, рoзумiти їх cтaтуc тa прaвoвe пoлoжeння HБУ, oргaнoм дeржaви, який єдиний мaє cпeцiaльну кoмпeтeнцiєю у cфeрi упрaвлiння бaнкiвcькoю cиcтeмoю. Укрaїнa зa вciмa пeрeлiчeними фaктoрaми cтикaєтьcя з прoблeмaтикoю брaку зoвнiшнiх cтимулiв.Effіcіency оf аn ecоnоmy оf аny cоuntry іs stіpulаted by stаbіlіty оf а nаtіоnаl currency аnd relіаbіlіty оf а bаnk system. Develоpment оf the bаnk sectоr іs mоstly determіned by аn іnfl uence оf externаl fаctоrs, і.e. а rоle оf а cоuntry, legіslаtіоn аnd effі cіency оf а cоurt system, rules оf trаnspаrency, requіrements fоr quаlіty оf repоrts, іndependence аnd prоfessіоnаlіsm оf а centrаl bаnk, аnd quаlіty оf cоrpоrаte mаnаgement. Tо suppоrt stаbіlіty аnd ecоnоmіc іndependence оf the cоuntry, there іs а need tо precіsely understаnd whаt elements аre cоmpоnents оf the bаnk system, whаt stаtus hаve these elements, аnd whаt legаl stаtus hаs the Nаtіоnаl Bаnk оf Ukrаіne, whіch іs the оnly stаte аuthоrіty endued wіth specіаl cоmpetence іn the bаnk mаnаgement sectоr. Frоm the аll mentіоned fаctоrs’ pоіnt оf vіew Ukrаіne deаls wіth the prоblems аnd оvercоmes lаck оf externаl іncentіves

Tracking Polypeptide Folds on the Free Energy Surface: Effects of the Chain Length and Sequence

Characterization of the folding transition in polypeptides and assessing the thermodynamic stability of their structured folds are of primary importance for approaching the problem of protein folding. We use molecular dynamics simulations for a coarse grained polypeptide model in order to (1) obtain the equilibrium conformation diagram of homopolypeptides in a broad range of the chain lengths, <i>N</i> = 10, ..., 100, and temperatures, <i>T</i> (in a multicanonical ensemble), and (2) determine free energy profiles (FEPs) projected onto an optimal, so-called “natural”, reaction coordinate that preserves the height of barriers and the diffusion coefficients on the underlying free energy hyper-surface. We then address the following fundamental questions. (i) How well does a kinetically determined free energy landscape of a single chain represent the polypeptide equilibrium (ensemble) behavior? In particular, under which conditions might the correspondence be lost, and what are the possible implications for the folding processes? (ii) How does the free energy landscape depend on the chain length (homopolypeptides) and the monomer interaction sequence (heteropolypeptides)? Our data reveal that at low <i>T</i> values equilibrium structures adopted by relatively short homopolypeptides (<i>N</i> < 60) are dominated by α-helical folds which correspond to the primary and secondary minima of the FEP. In contrast, longer homopolypeptides (<i>N</i> > 70), upon quasi-equilibrium cooling, fold preferentially in β-bundles with small helical portions, while the FEPs exhibit no distinct global minima. Moreover, subject to the choice of the initial configuration, at sufficiently low <i>T</i>, essentially metastable structures can be found and prevail far from the true thermodynamic equilibrium. We also show that, by sequence-enabling the polypeptide model, it is possible to restrict the chain to a very specific part of the configuration space, which results in substantial simplification and smoothing of the free energy landscape as compared to the case of the corresponding homopolypeptide

Protein Aggregation: Kinetics versus Thermodynamics

In this study, we address the questions of how important is the kinetics in protein aggregation, and what are the intrinsic properties of proteins that cause this behavior. On the basis of our recent quantitative calculation of the equilibrium phase diagram of natively folded α-helical and β-sheet forming peptides, we perform molecular dynamics simulations to demonstrate how the aggregation mechanism and end product depend on the temperature, concentration, and starting point in the phase diagram. The results obtained show that there are severe differences between the thermodynamically predicted and the kinetically obtained aggregate structures. The observed differences help to rationalize the suggestion that monomeric proteins in their native functional structure can be metastable with respect to the amyloid state, and that the native fold is a special property that protects them from aggregation

Tracking Polypeptide Folds on the Free Energy Surface: Effects of the Chain Length and Sequence

Characterization of the folding transition in polypeptides and assessing the thermodynamic stability of their structured folds are of primary importance for approaching the problem of protein folding. We use molecular dynamics simulations for a coarse grained polypeptide model in order to (1) obtain the equilibrium conformation diagram of homopolypeptides in a broad range of the chain lengths, <i>N</i> = 10, ..., 100, and temperatures, <i>T</i> (in a multicanonical ensemble), and (2) determine free energy profiles (FEPs) projected onto an optimal, so-called “natural”, reaction coordinate that preserves the height of barriers and the diffusion coefficients on the underlying free energy hyper-surface. We then address the following fundamental questions. (i) How well does a kinetically determined free energy landscape of a single chain represent the polypeptide equilibrium (ensemble) behavior? In particular, under which conditions might the correspondence be lost, and what are the possible implications for the folding processes? (ii) How does the free energy landscape depend on the chain length (homopolypeptides) and the monomer interaction sequence (heteropolypeptides)? Our data reveal that at low <i>T</i> values equilibrium structures adopted by relatively short homopolypeptides (<i>N</i> < 60) are dominated by α-helical folds which correspond to the primary and secondary minima of the FEP. In contrast, longer homopolypeptides (<i>N</i> > 70), upon quasi-equilibrium cooling, fold preferentially in β-bundles with small helical portions, while the FEPs exhibit no distinct global minima. Moreover, subject to the choice of the initial configuration, at sufficiently low <i>T</i>, essentially metastable structures can be found and prevail far from the true thermodynamic equilibrium. We also show that, by sequence-enabling the polypeptide model, it is possible to restrict the chain to a very specific part of the configuration space, which results in substantial simplification and smoothing of the free energy landscape as compared to the case of the corresponding homopolypeptide

Tracking Polypeptide Folds on the Free Energy Surface: Effects of the Chain Length and Sequence

Characterization of the folding transition in polypeptides and assessing the thermodynamic stability of their structured folds are of primary importance for approaching the problem of protein folding. We use molecular dynamics simulations for a coarse grained polypeptide model in order to (1) obtain the equilibrium conformation diagram of homopolypeptides in a broad range of the chain lengths, <i>N</i> = 10, ..., 100, and temperatures, <i>T</i> (in a multicanonical ensemble), and (2) determine free energy profiles (FEPs) projected onto an optimal, so-called “natural”, reaction coordinate that preserves the height of barriers and the diffusion coefficients on the underlying free energy hyper-surface. We then address the following fundamental questions. (i) How well does a kinetically determined free energy landscape of a single chain represent the polypeptide equilibrium (ensemble) behavior? In particular, under which conditions might the correspondence be lost, and what are the possible implications for the folding processes? (ii) How does the free energy landscape depend on the chain length (homopolypeptides) and the monomer interaction sequence (heteropolypeptides)? Our data reveal that at low <i>T</i> values equilibrium structures adopted by relatively short homopolypeptides (<i>N</i> < 60) are dominated by α-helical folds which correspond to the primary and secondary minima of the FEP. In contrast, longer homopolypeptides (<i>N</i> > 70), upon quasi-equilibrium cooling, fold preferentially in β-bundles with small helical portions, while the FEPs exhibit no distinct global minima. Moreover, subject to the choice of the initial configuration, at sufficiently low <i>T</i>, essentially metastable structures can be found and prevail far from the true thermodynamic equilibrium. We also show that, by sequence-enabling the polypeptide model, it is possible to restrict the chain to a very specific part of the configuration space, which results in substantial simplification and smoothing of the free energy landscape as compared to the case of the corresponding homopolypeptide

Tracking Polypeptide Folds on the Free Energy Surface: Effects of the Chain Length and Sequence

Characterization of the folding transition in polypeptides and assessing the thermodynamic stability of their structured folds are of primary importance for approaching the problem of protein folding. We use molecular dynamics simulations for a coarse grained polypeptide model in order to (1) obtain the equilibrium conformation diagram of homopolypeptides in a broad range of the chain lengths, <i>N</i> = 10, ..., 100, and temperatures, <i>T</i> (in a multicanonical ensemble), and (2) determine free energy profiles (FEPs) projected onto an optimal, so-called “natural”, reaction coordinate that preserves the height of barriers and the diffusion coefficients on the underlying free energy hyper-surface. We then address the following fundamental questions. (i) How well does a kinetically determined free energy landscape of a single chain represent the polypeptide equilibrium (ensemble) behavior? In particular, under which conditions might the correspondence be lost, and what are the possible implications for the folding processes? (ii) How does the free energy landscape depend on the chain length (homopolypeptides) and the monomer interaction sequence (heteropolypeptides)? Our data reveal that at low <i>T</i> values equilibrium structures adopted by relatively short homopolypeptides (<i>N</i> < 60) are dominated by α-helical folds which correspond to the primary and secondary minima of the FEP. In contrast, longer homopolypeptides (<i>N</i> > 70), upon quasi-equilibrium cooling, fold preferentially in β-bundles with small helical portions, while the FEPs exhibit no distinct global minima. Moreover, subject to the choice of the initial configuration, at sufficiently low <i>T</i>, essentially metastable structures can be found and prevail far from the true thermodynamic equilibrium. We also show that, by sequence-enabling the polypeptide model, it is possible to restrict the chain to a very specific part of the configuration space, which results in substantial simplification and smoothing of the free energy landscape as compared to the case of the corresponding homopolypeptide

Analysis of the evolution of the structure of the oligomers over 11 independent simulations.

<p>(A) Development of the fraction of polypeptide chains in a oligomer (black), fraction of polypeptide chains in a oligomer that form a <i>β</i>-sheet conformation (blue), fraction of hydrogen bonds in a oligomer in a <i>α</i>-helical conformation (orange), and in a <i>β</i>-sheet conformation (red), or otherwise (green). (B) Development of the distribution function of the average number of <i>β</i>-sheets 〈<i>N_n</i>〉 of size <i>n</i> at <i>t</i> = 1000 (black), <i>t</i> = 5000 (red), <i>t</i> = 30 000 (blue). (C) Distribution function 〈<i>N_l</i>〉 of the number of protofilaments composed of <i>l</i> layers at <i>t</i> = 1000 (black), <i>t</i> = 15 000 (red), <i>t</i> = 30 000 (blue).</p

Time series of the energy per peptide as a function of the progress variable (<i>t</i>).

<p>Together with the total energy (red line), we show the contributions from the hydrogen bonding energy (blue line), and the hydrophobic energy (black line). The gradual emergence of the cross-<i>β</i> ordering from the initially disordered oligomeric assemblies is characterised by a significant increase in the weight of the hydrogen bonding energy. Errorbars represent standard deviations over 11 independent trajectories. Representative structures formed during the process of conversion of the disordered oligomer into an amyloid-like structure are also shown at <i>t</i> = 5000, <i>t</i> = 15 000, and <i>t</i> = 30 000. The color code is as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000222#pcbi-1000222-g001" target="_blank">Figure 1</a>.</p

Histogram of the number <i>N_n</i> of <i>β</i>-sheets consisting of <i>n</i> peptides at four successive stages of the growth and reordering process of the oligomeric assembly shown in Figure 1: (A) <i>t</i> = 10 000, (B) <i>t</i> = 15 000, (C) <i>t</i> = 20 000, (d) <i>t</i> = 30 000).

<p>This plot shows how <i>β</i>-sheet assemblies are progressively formed by the growth and alignment of individual <i>β</i>-sheets. At <i>t</i> = 10 000 (A) there are six <i>β</i>-sheets of sizes ranging from 3 to 16, whereas at <i>t</i> = 30 000 (D), there are nine <i>β</i>-sheets of sizes ranging from 8 to 42. If <i>β</i>-sheets are aligned so that the angle between them is smaller than 20 degrees, they are considered to form a protofilament-like structure, and the corresponding bars in the histogram are shown with the same color, as for instance in the case of the red assembly (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000222#pcbi-1000222-g001" target="_blank">Figure 1c</a>, right), formed by four <i>β</i>-sheets of size 8, 19, 38, and 42.</p

Illustration of the self-assembly process of peptides into amyloid-like assemblies.

<p>All simulations were carried out at a concentration <i>c</i> = 12.5 mM and reduced temperature <i>T</i>* = 0.66. The progress variable <i>t</i> corresponds to the number of Monte Carlo moves performed in the simulation, and one unit of <i>t</i> is a series of 10⁵ Monte Carlo moves. Initially, at <i>t</i> = 1000 (A), all peptides are in a solvated state. As the simulation progresses, at <i>t</i> = 5000 (B), a hydrophobic collapse causes the formation of a disordered oligomer, which subsequently undergoes a structural reorganization into an amyloid-like assembly, at <i>t</i> = 30 000 (C), driven by the formation of ordered arrays of hydrogen bonds. Peptides that do not form intermolecular hydrogen bonds are shown in blue, while peptides that form intermolecular hydrogen bonds are assigned a random color, which is the same for peptides that belong to same <i>β</i>-sheet.</p