title: Novel homodimer model of the β-adrenergic receptor in complex with free fatty acids and cholesterol: first-principles calculation studies.
abstract: We propose a theoretical novel homodimer model of the β- adrenergic receptor (βAR) 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 bAR 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 bAR 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.
authors.affiliation: Department of Chemistry, Rikkyo University, Nishi-ikebukuro, Toshimaku, Tokyo 171-8501, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tokiwa