ID 6507
フルテキストファイル
著者
Fujiwara, Shin-ichi Department of Biological Regulation, Faculty of Medicine, Tottori University 研究者総覧 KAKEN
Amisaki, Takashi Department of Biological Regulation, Faculty of Medicine, Tottori University 研究者総覧 KAKEN
キーワード
molecular dynamics simulations
human serum albumin
fatty acid
conformational changes
drug‐binding site
principal component analysis
抄録
Human serum albumin (HSA) binds with fatty acids under normal physiologic conditions. To date, there is little published information on the tertiary structure of HSA-fatty acid complex in aqueous solution. In the present study, we used molecular dynamics (MD) simulations to elucidate possible structural changes of HSA brought about by the binding of fatty acids. Both unliganded HSA and HSA-fatty acid complex models for MD calculations were constructed based on the X‐ray crystal structures. Five myristates (MYRs) were bound in the HSA-fatty acid complex model. In the present MD study, the motion of domains I and III caused by the binding of MYR molecules increased the radius of gyration of HSA. Root‐mean‐square fluctuations from the MD simulations revealed that the atomic fluctuations of the specific amino acids at drug‐binding site I that can regulate the drug‐binding affinity were increased by the binding of MYR molecules. Primary internal motions, characterized by the first three principal components, were observed mainly at domains I and III in the principal component analysis for trajectory data. The directional motion projected on the first principal component of unliganded HSA was conserved in HSA-MYR complex as the third principal directional motion with higher frequency. However, the third principal directional motion in unliganded HSA turned into the first principal directional motion with lower frequency in the HSA-MYR complex. Thus, the present MD study provides insights into the possible conformational changes of HSA caused by the binding of fatty acids. Proteins 2006. © 2006 Wiley‐Liss, Inc.
出版者
Wiley‐Liss, Inc.
資料タイプ
学術雑誌論文
外部リンク
ISSN
10970134
書誌ID
AA11626960
掲載誌名
Proteins : structure, function, and genetics
64
3
開始ページ
730
終了ページ
739
発行日
2006-07-07
出版者DOI
著者版フラグ
著者版
著作権表記
Copyright © 2006 Wiley‐Liss, Inc.
掲載情報
This is the peer reviewed version of the following article: Shin-ichi Fujiwara, Takashi Amisaki.. Molecular dynamics study of conformational changes in human serum albumin by binding of fatty acids. Proteins : structure, function, and genetics . 2006, 64(3), 730-739. https://doi.org/10.1002/cssc.201500819 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
部局名
医学部・医学系研究科・医学部附属病院
言語
英語