MD Simulations on the Influence of Disease-Related Amino Acid Mutations in the Human Prion Protein

Chem-Bio Informatics Journal

Kholmirzo Kholmurodov¹  Toshikazu Ebisuzaki¹  Yoshinori Hirano¹ 

[1] Advanced Computing Center, Computational Science Division, Institute of Physical and Chemical Research (RIKEN)

关键词: Molecular Dynamics Simulations;    分子動力学計算;    Proteins;    タンパク質;    Prions;    プリオン;    Creutzfeldt-Jakob Disease;    クロイツフェルト・ヤコブ病;    Hydrogen Bond Network;    水素結合ネットワーク;   

DOI  :  10.1273/cbij.3.86

学科分类：生物化学/生物物理

来源: Chem-Bio Informatics Society

【 摘 要 】

References(37)Cited-By(2)We have performed molecular dynamics simulations on the human prion protein to study the effect of point mutations in relation to the inherited form of Creutzfeldt-Jakob disease. Three model structures of the human prion protein are examined with a focus on their dynamics and conformational changes. Model 1 is an NMR structure of the globular domain (125-228) of a wild-type prion. The model consists of three α-helices and an anti-parallel β-sheet. Models 2 and 3 are mutant structures containing a Glu200→Asp and a Glu200→Lys substitution, respectively. These models are derived from NMR structures. The Glu200→Lys in model 3 is a disease-related amino acid exchange. The results of about 2-million time step calculations have shown that the globular domains of models 1 and 2 are stable, whereas, for model 3, we observe a partial unfolding and reorganization of the protein structure by insertion of the disease-related mutation Glu200→Lys.

【 授权许可】

Unknown