| Title: | Computer-aided rational design of novel EBF analogues with an aromatic ring |
| Author(s): | Wang S; Sun Y; Du S; Qin Y; Duan H; Yang X; |
| Address: | "Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China. Laboratory of Agro-products Quality Safety Risk Assessment, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China. hxduan@cau.edu.cn. Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China. yangxl@cau.edu.cn" |
| DOI: | 10.1007/s00894-016-3011-3 |
| ISSN/ISBN: | 0948-5023 (Electronic) 0948-5023 (Linking) |
| Abstract: | "Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-beta-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized pi-pi and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1-D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure. Graphical abstract The design strategy of new EBF analogues based on the OBP7 structure" |
| Keywords: | EBF analogues Insect behavior regulators Odorant binding protein Rational design Semiochemicals; |
| Notes: | "PubMed-not-MEDLINEWang, Shanshan Sun, Yufeng Du, Shaoqing Qin, Yaoguo Duan, Hongxia Yang, Xinling eng Research Support, Non-U.S. Gov't Germany 2016/06/03 J Mol Model. 2016 Jun; 22(6):144. doi: 10.1007/s00894-016-3011-3. Epub 2016 Jun 1" |
