title: Unveiling the molecular mechanism of brassinosteroids: Insights from structure-based molecular modeling studies.
abstract: Brassinosteroid (BR) phytohormones play indispensable roles in plant growth and development. Brassinolide (BL) and 24-epibrassinolide (24-epiBL) are the most active ones among the BRs reported thus far. Unfortunately, the extremely low natural content and intricate synthesis process limit their popularization in agricultural production. Earlier reports to discover alternative compounds have resulted in molecules with nearly same scaffold structure and without diversity in chemical space. In the present study, receptors structure based BRs regulation mechanism was analyzed. First, we examined the detailed binding interactions and their dynamic stability between BL and its receptor BRI1 and co-receptor BAK1. Then, the binding modes and binding free energies for 24-epiBL and a series of representative BRs binding with BRI1 and BRI1-BAK1 were carried out by molecular docking, energy minimization and MM-PBSA free energy calculation. The obtained binding structures and energetic results provided vital insights into the structural factors affecting the activity from both receptors and BRs aspects. Subsequently, the obtained knowledge will serve as valuable guidance to build pharmacophore models for rational screening of new scaffold alternative BRs.
authors.affiliation: Center of Bioinformatics, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: leibl@nwsuaf.edu.cn.
authors.forename: Beilei
authors.initials: B
authors.lastname: Lei
authors.affiliation: Key Laboratory of Plant Protection Resources & Pest Management of the Ministry of Education, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yao
mesh_terms: D060406:Brassinosteroids / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D060406:Brassinosteroids
keywords: BAK1; BRI1; Binding free energy; Brassinosteroids; Molecular docking