Kazuyoshi Ueda

Structural reorganization of molecular sheets derived from cellulose II by molecular dynamics simulations

We investigated structural reorganization of two different kinds of molecular sheets derived from the cellulose II crystal using molecular dynamics (MD) simulations, in order to identify the initial structure of the cellulose crystal in the course of its regeneration process from solution. After a one-nanosecond simulation, the molecular sheet formed by van der Waals forces along the (11 0) crystal plane did not change its structure in an aqueous environment, while the other one formed by hydrogen bonds along the (110) crystal plane changed into a van der Waals-associated molecular sheet, such as the former. The two structures that were calculated showed substantial similarities such as the high occupancy of intramolecular hydrogen bonds between O3(H) and O5 of over 0.75, few intermolecular hydrogen bonds, and the high occurrence of hydrogen bonding with water. The convergence of the two structures into one denotes that the van der Waals-associated molecular sheet can be the initial structure of the cellulose crystal formed in solution. The main chain conformations were almost the same as those in the cellulose II crystal except for a -16 degrees shift of phi (dihedral angle of O5-C1-O1-C4) and the gauche-gauche conformation of the hydroxymethyl side group appears probably due to its hydrogen bonding with water. These results suggest that the van der Waals-associated molecular sheet becomes stable in an aqueous environment with its hydrophobic inside and hydrophilic periphery. Contrary to this, a benzene environment preferred a hydrogen-bonded molecular sheet, which is expected to be the initial structure formed in benzene.

The effect of hydration upon the conformation and dynamics of neocarrabiose, a repeat unit of β‐carrageenan

Molecular mechanics calculations have been performed for the disaccharide neocarrabiose, one of the repeat units of β‐carrageenan, as a general model for the (1 → 3)‐linkage in the carrageenans. An adiabatic conformational energy map for this molecule has been prepared by constrained energy minimization and compared to previously reported relaxed maps. Neither the experimentally determined crystal structure of neocarrabiose nor the fiber diffraction conformation of β‐carrageenan is a low energy conformation on the relaxed Ramachandran map. Molecular dynamics simulations in vacuum produced trajectories consistent with this relaxed vacuum surface. However, a simulation with explicitly included solvent water molecules produced a trajectory that remained in the region of the two experimental structures. This dramatic solvation effect is apparently the result of the breaking of an interring hydrogen bond between the O2 hydroxyl groups of neocarrabiose as both groups hydrogen bond to solvent.

The origin of the generalized anomeric effect: possibility of CH/n and CH/pi hydrogen bonds

Ab initio MO calculations were carried out at the MP4/6-311++G(3df,3pd)//MP2/6-311++G(3df,3pd) level to investigate the conformational Gibbs energy of a series of methyl ethers CH(3)O-CH(2)-X (X=OH, OCH(3), F, Cl, Br, CN, C triple bond CH, C(6)H(5), CHO). It was found that the Gibbs energy of the gauche conformers is lower in every case than that of the corresponding anti conformers. In the more stable gauche conformers, the interatomic distance between X and the hydrogen atom was shorter than the sum of the van der Waals radii. The natural bonding orbital (NBO) charges of group X were more negative in the gauche conformers than in the anti conformers. We suggest that the CH/n and CH/pi hydrogen bonds play an important role in stabilizing the gauche conformation of these compounds.

Current-voltage behavior in hole-only single-carrier devices with self-assembling dipole molecules on indium tin oxide anodes

The authors report the use of chemically modified indium tin oxide (ITO) with different binding groups (–COCl and –PO2Cl2) of p-chlorobenzene derivatives forming effective monolayers to control the work function of ITO and hence to enhance the hole injection. The enhanced hole injection is studied by measuring current density–voltage (J-V) characteristics. The behavior of J-V characteristics caused by varying the ITO work function in hole-only single-carrier devices with a hole transport layer of N,N′-diphenyl-N,N′-bis(3-methylphenyl)-1,1′-biphenyl-4,4′-diamine is examined. Upon grafting with p-chlorophenylphosphoryl dichloride, the J-V characteristics show a space-charge-limited conduction behavior. Such modified ITO anodes lead to improvements in the device properties.

Molecular Dynamics Simulation of Bombolitin II in the Dipalmitoylphosphatidylcholine Membrane Bilayer

The orientation behavior of Bombolitin II (BLT2) in the dipalmitoylphosphatidylcholine membrane bilayer was investigated by using molecular-dynamics simulation. During the 20-ns simulation, the BLT2 began to tilt and finally reached the angle of 51° from the membrane-normal. The structure of the peptide formed the amphipathic α-helical structure during the entire simulation time. The peptide tilts with its hydrophobic side faced to the hydrophobic core of the bilayer. We analyzed the mechanism of the tilting behavior of the peptide associated with the membrane in detail. The analysis showed that the hydrogen-bond interaction and the electrostatic interaction were found to exist between Lys(12) and a lipid molecule. These interactions are considered to work as an important factor in tilting the peptide to the membrane-normal.

Structure and Orientation of Bovine Lactoferrampin in the Mimetic Bacterial Membrane as Revealed by Solid-State NMR and Molecular Dynamics Simulation

Bovine lactoferrampin (LFampinB) is a newly discovered antimicrobial peptide found in the N1-domain of bovine lactoferrin (268-284), and consists of 17 amino-acid residues. It is important to determine the orientation and structure of LFampinB in bacterial membranes to reveal the antimicrobial mechanism. We therefore performed (13)C and (31)P NMR, (13)C-(31)P rotational echo double resonance (REDOR), potassium ion-selective electrode, and quartz-crystal microbalance measurements for LFampinB with mimetic bacterial membrane and molecular-dynamics simulation in acidic membrane. (31)P NMR results indicated that LFampinB caused a defect in mimetic bacterial membranes. Ion-selective electrode measurements showed that ion leakage occurred for the mimetic bacterial membrane containing cardiolipin. Quartz-crystal microbalance measurements revealed that LFampinB had greater affinity to acidic phospholipids than that to neutral phospholipids. (13)C DD-MAS and static NMR spectra showed that LFampinB formed an α-helix in the N-terminus region and tilted 45° to the bilayer normal. REDOR dephasing patterns between carbonyl carbon nucleus in LFampinB and phosphorus nuclei in lipid phosphate groups were measured by (13)C-(31)P REDOR and the results revealed that LFampinB is located in the interfacial region of the membrane. Molecular-dynamics simulation showed the tilt angle to be 42° and the rotation angle to be 92.5° for Leu(3), which are in excellent agreement with the experimental values.

Supermolecular structure of cellulose/amylose blends prepared from aqueous NaOH solutions and effects of amylose on structural formation of cellulose from its solution

We previously proposed a mechanism for the structural formation of cellulose from its solution using a molecular dynamics (MD) simulation and suggested that the initial structure from its solution plays a critical role in determining its final structure. Structural changes in the van der Waals-associated cellulose molecular sheet as the initial structure were examined by MD simulation; the molecular sheet was found to be disordered due to maltohexaoses as an amylose model in terms of the hydrogen bonding system of cellulose. The structure and properties of cellulose/amylose blends prepared from an aqueous NaOH solution were examined experimentally by wide-angle X-ray diffraction and dynamic viscoelasticity measurements. The crystallinity of cellulose in the cellulose/amylose blend films was lower than that of cellulose film. The diffraction peaks of the cellulose/amylose blends were slightly shifted; specifically, (1 1 0) was shifted to a higher angle, and (1 1 0) and (0 2 0) were shifted to lower angles. These experimental results probably resulted from the disordered molecular sheet, as revealed by MD simulations.

Structure and orientation of antibiotic peptide alamethicin in phospholipid bilayers as revealed by chemical shift oscillation analysis of solid state nuclear magnetic resonance and molecular dynamics simulation

The structure, topology and orientation of membrane-bound antibiotic alamethicin were studied using solid state nuclear magnetic resonance (NMR) spectroscopy. (13)C chemical shift interaction was observed in [1-(13)C]-labeled alamethicin. The isotropic chemical shift values indicated that alamethicin forms a helical structure in the entire region. The chemical shift anisotropy of the carbonyl carbon of isotopically labeled alamethicin was also analyzed with the assumption that alamethicin molecules rotate rapidly about the bilayer normal of the phospholipid bilayers. It is considered that the adjacent peptide planes form an angle of 100° or 120° when it forms α-helix or 310-helix, respectively. These properties lead to an oscillation of the chemical shift anisotropy with respect to the phase angle of the peptide plane. Anisotropic data were acquired for the 4 and 7 sites of the N- and C-termini, respectively. The results indicated that the helical axes for the N- and C-termini were tilted 17° and 32° to the bilayer normal, respectively. The chemical shift oscillation curves indicate that the N- and C-termini form the α-helix and 310-helix, respectively. The C-terminal 310-helix of alamethicin in the bilayer was experimentally observed and the unique bending structure of alamethicin was further confirmed by measuring the internuclear distances of [1-(13)C] and [(15)N] doubly-labeled alamethicin. Molecular dynamics simulation of alamethicin embedded into dimyristoyl phophatidylcholine (DMPC) bilayers indicates that the helical axes for α-helical N- and 310-helical C-termini are tilted 12° and 32° to the bilayer normal, respectively, which is in good agreement with the solid state NMR results.

Role of aromatic residues in amyloid fibril formation of human calcitonin by solid-state 13C NMR and molecular dynamics simulation

Calcitonin (CT) is an amyloid fibril forming peptide. Since salmon calcitonin (sCT), having Leu residues (Leu12, Leu16 or Leu19) instead of Tyr12, Phe16 or Phe19 for human calcitonin (hCT), is known to form the fibrils much slower than hCT, hCTs mutated to Leu residues at the position of 16 (F16L-hCT), 19 (F19L-hCT), and 12, 16 and 19 (TL-hCT) were examined to reveal the role of aromatic side-chains on amyloid fibrillation using solid-state (13)C NMR. The detailed kinetics were analyzed using a two-step reaction mechanism such as nucleation and fibril elongation with the rate constants of k1 and k2, respectively. The k2 values of hCT mutants were significantly slower than that of hCT at a neutral pH, although they were almost the same at an acidic pH. The (13)C chemical shifts of the labeled sites showed that the conformations of monomeric hCT mutants take α-helices as viewed from the Gly10 moiety. The hCT mutants formed fibrils and during the fibril formation, the α-helix around Gly10-Phe22 changed to the β-sheet, and the major structures around Ala26-Ala31 were random coil in the fibrils. Molecular dynamics simulation was performed for the β-sheet system of hCT9-23 and its mutants F16L-hCT9-23, F19L-hCT9-23 and TL-hCT9-23. In one of the stable fibril structures, Phe16 of hCT interacts with Phe19 of the next strand alternatively. In the hCT mutants, lack of Phe16 and Phe19 interaction causes significant instability as compared with the hCT fibril, leading to the reduction of k2 values, as observed experimentally in the hCT mutants at a neutral pH.

Dynamic Structure of Bombolitin II Bound to Lipid Bilayers as Revealed by Solid-state NMR and Molecular-Dynamics Simulation

Bombolitin II (BLT2) is one of the hemolytic heptadecapeptides originally isolated from the venom of a bumblebee. Structure and orientation of BLT2 bound to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membranes were determined by solid-state (31)P and (13)C NMR spectroscopy. (31)P NMR spectra showed that BLT2-DPPC membranes were disrupted into small particles below the gel-to-liquid crystalline phase transition temperature (T(c)) and fused to form a magnetically oriented vesicle system where the membrane surface is parallel to the magnetic fields above the T(c). (13)C NMR spectra of site-specifically (13)C-labeled BLT2 at the carbonyl carbons were observed and the chemical shift anisotropies were analyzed to determine the dynamic structure of BLT2 bound to the magnetically oriented vesicle system. It was revealed that the membrane-bound BLT2 adopted an α-helical structure, rotating around the membrane normal with the tilt angle of the helical axis at 33°. Interatomic distances obtained from rotational-echo double-resonance experiments further showed that BLT2 adopted a straight α-helical structure. Molecular dynamics simulation performed in the BLT2-DPPC membrane system showed that the BLT2 formed a straight α-helix and that the C-terminus was inserted into the membrane. The α-helical axis is tilted 30° to the membrane normal, which is almost the same as the value obtained from solid-state NMR. These results suggest that the membrane disruption induced by BLT2 is attributed to insertion of BLT2 into the lipid bilayers.