Phosphorylation reaction in cAPK protein kinase-free energy quantum mechanical/molecular mechanics simulations

We present results of a theoretical analysis of the phosphorylation reaction in cAMP-dependent protein kinase using a combined quantum mechanical and molecular mechanics (QM/MM) approach. Detailed analysis of the reaction pathway is provided using a novel QM/MM implementation of the nudged elastic band method, finite temperature fluctuations of the protein environment are taken into account using free energy calculations, and an analysis of hydrogen bond interactions is performed on the basis of calculated frequency shifts. The late transfer of the substrate proton to the conserved aspartate (D166), the activation free energy of 15 kcal/mol, and the slight exothermic (-3 kcal/mol) character of the reaction are all consistent with the experimental data. The near attack conformation of D166 in the reactant state is maintained by interactions with threonine-201, asparagine-177, and most notably by a conserved water molecule serving as a strong structural link between the primary metal ion and the D166. The secondary Mg ion acts as a Lewis acid, attacking the beta-gamma bridging oxygen of ATP. This interaction, along with a strong hydrogen bond between the D166 and the substrate, contributes to the stabilization of the transition state. Lys-168 maintains a hydrogen bond to a transferring phosphoryl group throughout a reaction process. This interaction increases in the product state and contributes to its stabilization.     

The Implications of (2S,4S)‐Hydroxyproline 4‐O‐Glycosylation for Prolyl Amide Isomerization

The conformations of peptides and proteins are often influenced by glycans O‐linked to serine (Ser) or threonine (Thr). (2S,4R)‐4‐Hydroxyproline (Hyp), together with L ‐proline (Pro), are interesting targets for O‐glycosylation because they have a unique influence on peptide and protein conformation. In previous work we found that glycosylation of Hyp does not affect the N‐terminal amide trans/cis ratios (K_trans/cis) or the rates of amide isomerization in model amides. The stereoisomer of Hyp—(2S,4S)‐4‐hydroxyproline (hyp)—is rarely found in nature, and has a different influence both on the conformation of the pyrrolidine ring and on K_trans/cis. Glycans attached to hyp would be expected to be projected from the opposite face of the prolyl side chain relative to Hyp; the impact this would have on K_trans/cis was unknown. Measurements of ³J coupling constants indicate that the glycan has little impact on the C^γ‐endo conformation produced by hyp. As a result, it was found that the D ‐galactose residue extending from a C^γ‐endo pucker affects both K_trans/cis and the rate of isomerization, which is not found to occur when it is projected from a C^γ‐exo pucker; this reflects the different environments delineated by the proline side chain. The enthalpic contributions to the stabilization of the trans amide isomer may be due to disruption of intramolecular interactions present in hyp; the change in enthalpy is balanced by a decrease in entropy incurred upon glycosylation. Because the different stereoisomers—Hyp and hyp—project the O‐linked carbohydrates in opposite spatial orientations, these glycosylated amino acids may be useful for understanding of how the projection of a glycan from the peptide or protein backbone exerts its influence.     

Synthesis and X-ray diffraction study of ternary ferrites LaNaMnFeO5 and LaKMnFeO5

Ferrites LaNaMnFeO₅ and LaKMnFeO₅ have been synthesized by the ceramic method from lanthanum(III) and iron(III) oxides and sodium and potassium carbonates. The ferrites crystallize in the orthorhombic crystal system with the following lattice parameters: LaNaMnFeO₅: a = 10.943 ± 0.002 Å, b = 11.022 ± 0.001 Å, c = 16.165 ± 0.028 Å, V ⁰ = 1949.72 ų, Z = 16, V _{unit cell} ⁰ = 12.1.85 ų, ρ_X = 4.83, ρ_pycn = 4.76 ± 0.09 g/cm³; LaKMnFeO₅: a = 10.959 ± 0.011 Å, b = 11.036 ± 0.005 Å, c = 17.825 ± 0.074 Å, V ⁰ = 2155.81 ų, Z = 16, V _{unit cell} ⁰ = 134.74 ų, ρ_X = 4.54, ρ_pycn = 4.46 ± 0.07 g/cm³.     

Mathematical modeling of methoxyanabasine C11H16N2O polymer solution ultrafiltration

This work covers the mathematical modeling of ultrafiltration with immobile membranes for physiologically-active of methoxyanabasine C₁₁H₁₆N₂O polymer solution. Methoxyanabasine is used as low toxic antineoplastic drug. On the basis of theoretical and experimental analysis of mass transfer and hydrodynamics, it is offered the mathematical model of permeability of membranes at an ultrafiltration of polymer solutions. Further the formulas for determination of factor of concentration polarization and ultrafiltration selectivity are calculated.     

Scientific Arkhangelsk and Pomorie: A Walk Through Centuries and Thousands of Miles

Even by Russian standards, the country’s northwestern territories contouring the White and Barents seas are vast, remote, and sparsely populated. Yet for seven centuries that faraway province has served as a nursery of religious and intellectual freedom and as a primary entry point for Western civilization and trade, containing several scientific landmarks of interest to the physical tourist. This article is intended as a concise guide to the scientifically relevant attractions in the city of Arkhangelsk and in relatively “nearby” locations that can be reached within reasonable time and with reasonable convenience; these include Mikhail Lomonosov’s birthplace on Kholmogory and the Solovetsky islands. We will also briefly mention relevant facts for the somewhat more remote—but still within 1000 km—territories of Kola peninsula and the Novaya Zemlya islands.     

Temperature Dependence of the Proton Overhauser DNP Enhancements on Aqueous Solutions of Fremy’s Salt Measured in a Magnetic Field of 9.2?T

The temperature dependence of the water-proton dynamic nuclear polarization (DNP) enhancement from Fremy’s salt nitroxide radicals was measured in a magnetic field of 9.2?T (corresponding to 260?GHz microwave (MW) and 392?MHz NMR frequencies) in the temperature range of 15–65?°C. The temperature could be determined directly from the proton NMR line shift of the sample. Very high DNP enhancements of ?38 (signal integral) or ?81 (peak intensity) could be achieved with a high-power gyrotron MW source. The experimental findings are compared with classical Overhauser theory for liquids, which is based on the translational and rotational motion of the molecules and with molecular dynamics calculations of the coupling factor.     

Direct deposition of chitosan macromolecules on a substrate from solutions in supercritical carbon dioxide: Solubility and conformational analysis

Chitosan and its derivatives are promising materials for coating medical devices because this procedure improves their bio- and haemocompatibility. It is known that supercritical carbon dioxide attracts significant scientific interest in biomedical applications as well. Coatings deposited directly from solutions in supercritical carbon dioxide are expected to have particularly smooth and uniform morphology that should enhance their stability. We have tested the possibility of obtaining chitosan films using direct deposition from solutions in this fluid. In order to reveal benefits of this approach we modelled and studied the initial stage of formation of chitosan coatings with prototype system of depositing pioneer single polymer chains directly from such solutions on a model ultrasmooth mica substrate. We estimated achievable solubility of the chitosan materials in supercritical carbon dioxide and performed conformational analysis of the deposited chitosan chains on a substrate. AFM imaging directly demonstrated that the pioneer macromolecules adsorb as rather extended 2D coils from such solutions.     

Study of ion specific interactions of alkali cations with dicarboxylate dianions

Alkali metal cations often show pronounced ion-specific interactions and selectivity with macromolecules in biological processes, colloids, and interfacial sciences, but a fundamental understanding about the underlying microscopic mechanism is still very limited. Here we report a direct probe of interactions between alkali metal cations (M(+)) and dicarboxylate dianions, (-)O(2)C(CH(2))(n)CO(2)(-) (D(n)(2-)) in the gas phase by combined photoelectron spectroscopy (PES) and ab initio electronic structure calculations on nine M(+)-D(n)(2-) complexes (M = Li, Na, K; n = 2, 4, 6). PES spectra show that the electron binding energy (EBE) decreases from Li(+) to Na(+) to K(+) for complexes of M(+)-D(2)(2-), whereas the order is Li(+) < Na(+) ≈ K(+) when M(+) interacts with a more flexible D(6)(2-) dianion. Theoretical modeling suggests that M(+) prefers to interact with both ends of the carboxylate -COO(-) groups by bending the flexible aliphatic backbone, and the local binding environments are found to depend upon backbone length n, carboxylate orientation, and the specific cation M(+). The observed variance of EBEs reflects how well each specific dicarboxylate dianion accommodates each M(+). This work demonstrates the delicate interplay among several factors (electrostatic interaction, size matching, and strain energy) that play critical roles in determining the structures and energetics of gaseous clusters as well as ion specificity and selectivity in solutions and biological systems.     

A revised mechanism of thermal decay of arylnitroso oxides

The electronic spectra were measured and the unimolecular decay kinetics of the isomeric forms (cis and trans) of 4-methoxyphenylnitroso oxide in acetonitrile, benzene, and hexane was studied using flash photolysis. The cis form absorbed in a shorter wavelength region and was more labile than the trans form. The difference between the reactivity of the two species increased on going from hexane to acetonitrile. The temperature dependences of reaction rate constants were studied for both isomeric forms. The analysis of products of flash photolysis of 4-methoxyphenyl azide in the presence of oxygen allowed for understanding the mechanism of thermal decay of nitroso oxides. It was shown that the trans nitroso oxide is converted into cis nitroso oxide. The latter undergoes an unusual ring cleavage reaction to form 4-methoxy-6-oxohexa-2,4-dienenitrile N-oxide derivative. We conclude that the nitro- and nitrosobenzenes, which are the main products of the steady-state photolysis of aromatic azides in the presence of oxygen, are formed by the photochemical transformation of the nitroso oxides.     

Polygones

We study the class of structures formed by all the polygons over a given monoid, which is equivalent to the study of the varieties in a language containing only unary functions. We collect and amplify previous results concerning their stability and superstability. Then we characterize the regular monoids for which all these polygons are ω-stable; the question about the existence of a non regular monoid with this property is left open.