[3P-1] Poster 3 (3P-01ー3P-47)

[3P-46] Amyloid-fibril disruption by the infrared-free electron laser observed by nonequilibrium molecular dynamics simulations

^○Hisashi Okumura^1,2,3, Satoru Itoh^1,2,3, Kazuhiro Nakamura⁴, Takayasu Kawasaki^5,6 (1.ExCELLS, 2.IMS, 3.SOKENDAI, 4.Gunma Univ., 5.Tokyo University of Science, 6.KEK)

We performed nonequilibrium molecular dynamics simulations, in which an amyloid-β amyloid fibril was destroyed via infrared free-electron laser (IR-FEL) irradiation, and discovered a new mechanism, in which water molecules disrupt protein aggregates. The intermolecular hydrogen bonds formed by C=O and N-H in the fibril are broken at each pulse of laser irradiation. These bonds spontaneously reform after the irradiation in many cases. However, when a water molecule happens to enter the gap between C=O and N-H, it inhibits the reformation of the hydrogen bonds. Such sites become defects in the regularly aligned hydrogen bonds, from which all hydrogen bonds in the intermolecular β-sheet are broken as the fraying spreads. This role of water molecules is entirely different from other known mechanisms. Additionally, we found that helix structures form more after the amyloid disruption; this is because the resonance frequency is different in a helix structure. Our findings provide a theoretical basis for the application of IR-FEL to the future treatment of amyloidosis.