title: Computer-aided rational design of novel EBF analogues with an aromatic ring.
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)-β-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 π-π 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.
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory of Agro-products Quality Safety Risk Assessment, Institute of Agro-products Processing Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.
authors.forename: Yaoguo
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China. hxduan@cau.edu.cn.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China. yangxl@cau.edu.cn.
authors.forename: Xinling
authors.initials: X
authors.lastname: Yang
keywords: EBF analogues; Insect behavior regulators; Odorant binding protein; Rational design; Semiochemicals