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Title

Novel homodimer model of the ▀-adrenergic receptor in complex with free fatty acids and cholesterol: first-principles calculation studies

 

Authors

Yuka Nakano1, Yasuo Watanabe2, Yoshihiko Ito3, Shizuo Yamada3 & Hiroaki Tokiwa1*

 

Affiliation

1Department of Chemistry, Rikkyo University, Nishi-ikebukuro, Toshimaku, Tokyo 171-8501, Japan; 2Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan; 3School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka 422-8526, Japan.

 

Email

tokiwa@rikkyo.ac.jp; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received November 13, 2012; Accepted November 14, 2012; Published December 19, 2012

 

Abstract

We propose a theoretical novel homodimer model of the ▀- adrenergic receptor (▀AR) in complex with a heterogeneous mixture of free fatty acids (FFAs) and cholesterol based on first-principles calculations. We used the density-functional-based tight binding with dispersion (DFTB-D) method, which accurately evaluates van der Waals interactions between FFAs and amino acid residues in the receptor. The calculations suggest that a stable homodimer of ?AR can form a complex with FFAs and cholesterol by extensive van der Waals interactions in the cell membrane, and that the heterogeneous composition of the FFAs is important for the stability of the homodimer complex. The stable van der Waals interactions propagate from one of the ?AR to the other through the cholesterol and FFAs in the homodimer complex. The energy propagation in the complex has the potential to enhance molecular signaling in adipocytes, because the stability of the complex can influence anti-adiposity effects after oral treatment of the FFA components.

 

Citation

Nakano et al. Bioinformation 8(25): 1245-1248 (2012)
 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.