Conformational dynamics of polypeptides and proteins in the dihedral angle space and in the cartesian coordinate space: Normal mode analysis of deca-alanine

Effects of different treatments of the degrees of freedom of bond length stretching and bond angle bending in computational analysis of conformational dynamics of proteins and polypeptides are assessed. More specifically, the normal mode analysis of conformational dynamics of α-helix of deca-alanine has been carried out both in the dihedral angle space (DAS) and in the Cartesian coordinate space (CCS). Almost perfect one-to-one correspondence has been found between normal modes in the CCS with frequencies less than 128 cm^?1 and those in the DAS with frequencies less than 164 cm^?1. Patterns of atomic displacements in the corresponding modes are very similar. This indicates that the effects of fixing degrees of freedom of bond length stretching and bond angle bending on the very-low-frequency normal modes in the CCS with frequencies less than 128 cm^?1 are almost solely to increase the frequencies by about 20%. The conclusion indicates that the different treatment of these degree does not lead to qualitatively different results as long as low-frequency motions are concerned. Based on the results of calculation, mechanical property of the α-helix of deca-alanine is discussed.     

Visualization studies using PIV in a cylindrical tank with and without vortex suppressor

Vortexing occurs during draining from tanks which reduces the rate of outflow. The phenomenon is augmented by initial rotation. The use of a vortex suppressor in a circular tank prevents vortexing. The reasons for the suppression of the vortexing are not clear. In this paper quantitative flow visualization results using PIV are presented which bring out the flow structure under various conditions. The suppressor leads to a faster decay in the rotational component.     

Hydration-dependent protein dynamics revealed by molecular dynamics simulation of crystalline staphylococcal nuclease

Molecular dynamics simulations of crystalline Staphylococcal nuclease in full and minimal hydration states were performed to study hydration effects on protein dynamics at temperatures ranging from 100 to 300 K. In a full hydration state (hydration ratio in weight, h=0.49), gaps are fully filled with water molecules, whereas only crystal waters are included in a minimal hydration state (h=0.09). The inflection of the atomic mean-square fluctuation of protein as a function of temperature, known as the glass-like transition, is observed at approximately 220 K in both cases, which is more significant in the full hydration state. By examining the temperature dependence of residual fluctuation, we found that the increase of fluctuations in the loop and terminal regions, which are exposed to water, is much greater than that in other regions in the full hydration state, but the mobilities of the corresponding regions are relatively restricted in the minimal hydration state by intermolecular contact. The atomic mean-square fluctuation of water molecules in the full hydration state at 300 K is 1 order of magnitude greater than that in the minimal hydration state. Above the transition temperature, most water molecules in the full hydration state behave like bulk water and act as a lubricant for protein dynamics. In contrast, water molecules in the minimal hydration state tend to form more hydrogen bonds with the protein, restricting the fluctuation of these water molecules to the level of the protein. Thus, intermolecular interaction and solvent mobility are important to understand the glass-like transition in proteins.     

Energy-gaining formation and catalytic behavior of active structures in a SiO(2)-supported unsaturated Ru complex catalyst for alkene epoxidation by DFT calculations

The formation and catalytic behavior of active structures in a SiO(2)-supported unsaturated Ru complex catalyst for alkene epoxidation were studied by means of hybrid density functional theory (DFT) calculations. An energy-gaining route for the catalyst activation was found to allow the formation of active unsaturated Ru complexes and the remarkable alkene epoxidation via an exothermic reaction path between isobutyraldehyde and oxygen. In the proposed Bartlett mechanism, Ru promotes the formation of peracid intermediate and facilitates the intermolecular hydrogen transfer in the peracid intermediate, while alkene molecules do not directly coordinate to the Ru site. It was found that stilbene epoxidation is easier to achieve than ethene epoxidation thanks to the electron donating phenyl groups.     

Transform and relax sampling for highly anisotropic systems: application to protein domain motion and folding

Transform and relax sampling (TRS) is proposed as a conformational sampling method to enhance "soft" fluctuation in highly anisotropic systems using molecular dynamics simulation. This method consists of three stages; transform, relax, and sampling. In the transform stage, molecular dynamics simulation is performed with randomly assigned force bias to enhance the fluctuations along relatively soft collective movements, as expected from the linear response theory. After relaxing the heated system to equilibrium without force bias in the relax stage, Monte Carlo-type determination is made as to whether the generated state is accepted or not. The sampling stage is then conducted for conformational sampling by conventional molecular dynamics simulation. TRS is first applied for the idealized multidimensional double-well C(α) model to mimic protein open-close transition. Subsequently, it is applied to three different all-atom protein systems in an explicit solvent model; T4 lysozyme, glutamine binding protein, and a mini-protein chignolin. Investigation of structural variations in the hinge angle of T4 lysozyme in crystals is demonstrated by TRS. The liganded close structure of the glutamine binding protein is sampled starting from the unliganded open form. Chignolin is shown to fold into a native structure multiple times starting from highly extended structures within 100 ns. It is concluded that TRS sampled a reasonable conformational space within a relatively short simulation time in these cases. Possible future extensions of TRS are also discussed.     

Synthesis of biantennary complex-type nonasaccharyl asn building blocks for solid-phase glycopeptide synthesis

The biantennary complex-type N-glycans bearing LacNAc and LacdiNAc as the nonreducing end motif were synthesized in a protected form suitable to use in the Fmoc solid-phase peptide synthesis studies. Two approaches for the nonasaccharide synthesis were examined by taking advantage of the highly β-selective glycosylation with GlcNTCA (N-phenyl)trifluoroacetimidate. An earlier approach, which involved the reaction of the trisaccharide donor (Gal-GlcNTCA-Man) and trisaccharide acceptor (Man-GlcNPhth(2)-N(3)), produced a mixture of nonasaccharide isomers. On the other hand, mannosylation of the trisaccharide acceptor (Man-GlcNPhth(2)-N(3)) stereoselectively afforded the known pentasaccharide (Man(3)-GlcNPhth(2)-N(3)), which was reacted with the disaccharyl glycosyl donor (Gal-GlcNTCA or GalNTCA-GlcNTCA) to produce the desired nonasaccharide as a single stereoisomer. Selective dephthaloylation followed by N-acetylation furnished the GlcNAc(2) functionality. The resulting nonasaccharyl azides were condensed with Fmoc-Asp(OPfp)-OBu(t) or Fmoc-Asp(OPfp)-OPac in the presence of Ph(CH(3))(2)P and HOOBt. Finally, the Zn reduction and cleavage of the tert-butyl ester or Zn reduction alone produced the targeted nonasaccharyl Asn building blocks.     

Chemo-enzymatic synthesis of a multi-useful chiral building block molecule for the synthesis of medicinal compounds

Optical resolution of 2-methyl-2-nitrobut-3-en-1-ol has been accomplished using a "low-temperature lipase-catalyzed transesterification" carried out at -40 °C.     

Incorporation of cationic electron donor of Ni-pyridyltetrathiafulvalene with anionic electron acceptor of polyoxometalate

A new salt-[Ni(II)(DMSO)(5)(TTFPy)](2)[α-SiW(12)O(40)] (1)-based on polyoxometalates was prepared by coordinating a cationic electron donor of pyridyltetrathiafulvalene (TTFPy) with Ni(II). Although the TTFPy molecule did not form a salt with the anionic α-[SiW(VI)(12)O(40)](4-) because of the weak charge-transfer (CT) interaction, the coordination of Ni with the pyridyl moiety permitted salt formation driven by electrostatic interaction, giving a single crystal of 1. Crystallographic analysis, UV-vis and IR spectroscopy and electrochemical characterization revealed that the fully oxidized α-[SiW(VI)(12)O(40)](4-) was crystallized with the neutral TTFPy moiety from the acetonitrile solution because of the low electron-withdrawing ability of α-[SiW(VI)(12)O(40)](4-), forming a brown-orange crystal. The crystal colour quickly turned to black by immersing in methanol, due to CT from TTF moiety to α-[SiW(VI)(12)O(40)](4-), which was caused by the solvent effect. Increase in the solvent acceptor number from 18.9 for acetonitrile to 41.3 for methanol resulted in the enhancement of the electron withdrawing ability of α-[SiW(VI)(12)O(40)](4-) by 0.317 V in methanol.     

Time-domain interferometry experiments using multi-line nuclear absorbers

Langmuir-Blodgett (LB) films of octadecanoyl hydroxamic acid (C18N) complexed with Fe^3?+? ions have been prepared at various subphase pH values. The LB films consisting of different number of layers were investigated by ⁵⁷Fe conversion electron M?ssbauer spectroscopy (CEM) at room temperature. The CEM detector contained a piece of α-iron, enriched with ⁵⁷Fe, using as an internal standard. The M?ssbauer pattern of the C18N/Fe LB films is a doublet with parameters δ = 0.35?mm/s and Δ = 0.74?mm/s. A gradual increase of the relative occurrence of the doublet compared to the sextet of the internal standard was observed with the increasing number of layers, indicating the nearly uniform distribution of Fe among the LB layers.