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Authors
Fujiwara, Shin-ichi Department of Biological Regulation, Faculty of Medicine, Tottori University Researchers DB KAKEN
Amisaki, Takashi Department of Biological Regulation, Faculty of Medicine, Tottori University Researchers DB KAKEN
Keywords
molecular dynamics simulations
human serum albumin
fatty acid
conformational changes
drug‐binding site
principal component analysis
Abstract
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.
Publisher
Wiley‐Liss, Inc.
Content Type
Journal Article
Link
ISSN・ISBN
10970134
NCID
AA11626960
Journal Title
Proteins : structure, function, and genetics
Volume
64
Issue
3
Start Page
730
End Page
739
Published Date
2006-07-07
Publisher-DOI
Text Version
Author
Rights
Copyright © 2006 Wiley‐Liss, Inc.
Citation
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.
Department
Faculty of Medicine/Graduate School of Medical Sciences/University Hospital
Language
English