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Theoretical and Computational Molecular Science Okumura Group

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Location: Myoudaiji, Computer Center Bldg. Room225
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Molecular Dynamics Simulation, Protein, Amyloid

Biomolecular Dynamics Simulation: Protein Folding, Denaturation, Aggregation, and Amyloid Fibril

Biomolecules such as proteins and peptides have complicated free-energy landscape with many local minima. The conventional canonical-ensemble molecular dynamics (MD) simulations tend to get trapped in a few of the local-minimum states. To overcome these difficulties, we have proposed new generalized-ensemble algorithms, such as replica-permutation method. We apply these methods to proteins and peptides and try to predict the native structures of proteins as in Figure 1.

We are also interested in amyloid fibrils, which are insoluble aggregates of misfolded fibrous proteins and associated with more than 20 human neurodegenerative diseases (Figure 2). For example, Alzheimer’s disease is related to amyloid-β (Aβ) peptides. To overcome these diseases, it is essential to understand amyloid genesis and disruption. We perform such MD simulations of amyloid fibrils.

2018_okumura.pngFig. 1 (a) Free-energy landscape and (b) typical structures at local-minimum free-energy states of C-peptide.

2015oku_2.jpgFig.2 Disruption process of an amyloid fibril of Aβ peptides by supersonic wave. The amyloid fibril is disrupted when a bubble collapses.

Selected Publications

  1. H. Okumura and S. G. Itoh, “Structural and fluctuational difference between two ends of Aβ amyloid fibril: MD simulation predicts only one end has open conformations”, Sci. Rep. 6, 38422 (9 pages) (2016).
  2. S. G. Itoh and H. Okumura, “Oligomer formation of amyloid-β(29-42) from its monomers using the Hamiltonian replica-permutation molecular dynamics simulation”, J. Phys. Chem. B 120, 6555-6561 (2016).
  3. H. Okumura and S. G. Itoh, “Amyloid fibril disruption by ultrasonic cavitation: Nonequilibrium molecular dynamics simulations,” J. Am. Chem. Soc. 136, 10549-10552 (2014).
  4. S. G. Itoh and H. Okumura: “Replica-permutation method with the Suwa-Todo algorithm beyond the replica-exchange method”, J. Chem. Theory Comput. 9, 570-581 (2013).