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.

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Temperature dependencies of the optical rotation and size exclusion chromatography with low-angle laser light scattering (SEC−LALLS) were performed on the sonicated K+, κ-carrageenan in KCl salt solutions. The molecular weights were measured at the temperatures of the coil, helix, and coil−helix transition regions. The temperature at each region was determined by the optical rotation experiment. In a solution of low KCl salt concentration, the molecular weights did not change at any of the temperatures investigated. In this case, no hysteresis in the temperature dependence curve of optical rotation was observed. On the other hand, when the salt concentration increased, the molecular weight increased according to the transition from the coil to a helical conformation. In this case, a hysteresis was observed in the optical rotation curve. Moreover, the greater the increase in the KCl concentration, the greater the increase in molecular weight. These results indicate the existence of multiple conformational states for κ-carrageenan that depend upon the solution conditions. That is, κ-carrageenan makes a conformational transition from the coil to a single helical conformation at low KCl salt concentrations. However, κ-carrageenan takes on a helical conformation with a dimerized molecular weight when the salt concentration increases. These dimerized helical molecules further aggregate when the salt concentration increases further.

Molecular dynamics (MD) calculations have been carried out by using the CHARMM program to study initial decomposition processes in nitramines (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) polymorphs and related nitramines) in the crystalline state. Three types of simulations with different conditions were performed to investigate the effect of the crystalline state on the decomposition processes of the molecule. When the simulation was performed with the gas phase value of the equilibrium N−N bond length but started from the crystallographic structure as an initial conformation, which mimics the course of the trajectory from the crystal state to the gas phase, large amplitude oscillations of the N−N bond lengths were observed in the trajectories. Another simulation, which takes the crystal effects into account by adjusting the equilibrium N−N bond length in CHARMM, also showed the large amplitude oscillations of the N−N bond. In this case, it was also observed that excess vibrational energy of N−NO2 is transferred to another N−NO2 moiety. These results indicate the importance of compressed N−N bonds in the crystal for bringing about the initial decomposition process of nitramines.