caa a22 4500 445878738 CHVBK 20180317145535.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s11030-011-9311-8 doi (NATIONALLICENCE)springer-10.1007/s11030-011-9311-8 Insights into the binding modes of human β3-adrenergic receptor agonists with ligand-based and receptor-based methods [Elektronische Daten] [Fangfang Jin, Chunhua Lu, Xianqiang Sun, Weihua Li, Guixia Liu, Yun Tang] Agonists of β3-adrenergic receptor (AR) have been thought as potential drugs for the treatment of obesity, type II diabetes, and overactive bladder. In order to clarify the essential structure-activity relationship and the detailed binding modes of β3-AR agonists as well as to identify new lead compounds activating β3-AR, ligand-based and receptor-based methods were applied. The pharmacophore models were developed based on 144 β3-AR agonists. Meanwhile, the homology model of the β3-AR was built based on the crystal structure of β2-AR. The pharmacophore model and the homology model mapped with each other very well, and some important information was obtained from the docking result. For example, agonists formed similar hydrogen-bonding interactions with residues Asp117, Arg315, and Asn332, π-π stacking interaction with residues Phe308, and hydrophobic interactions with residues Val118, Val121, Ala197, Phe198, Ala199, Phe309, and Phe328 of β3-AR. And the major difference about binding mode from the crystal structures of β1- and β2-ARs is the hydrogen-bonding interaction with the residue Arg315, which corresponds to the residue Asn313 of β1-AR and the residue His296 of β2-AR, respectively. Our findings may be crucial for the design and development of novel selective and potent β3-AR agonists. Springer Science+Business Media B.V., 2011 β-Adrenergic receptor nationallicence Pharmacophore modeling nationallicence Holomogy modeling nationallicence Molecular docking nationallicence β3-Adrenergic receptor agonist nationallicence Jin Fangfang School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut Lu Chunhua School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut Sun Xianqiang School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut Li Weihua School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut Liu Guixia School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut Tang Yun School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut Molecular Diversity Springer Netherlands 15/4(2011-11-01), 817-831 1381-1991 15:4<817 2011 15 11030 https://doi.org/10.1007/s11030-011-9311-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-011-9311-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jin Fangfang School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut NATIONALLICENCE 700 1- Lu Chunhua School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut NATIONALLICENCE 700 1- Sun Xianqiang School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut NATIONALLICENCE 700 1- Li Weihua School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut NATIONALLICENCE 700 1- Liu Guixia School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut NATIONALLICENCE 700 1- Tang Yun School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, 200237, Shanghai, China aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/4(2011-11-01), 817-831 1381-1991 15:4<817 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer