ABSTRACT
Brassinosteroids (BRs) are essential phytohormones, which bind to the plant receptor, BRI1, to regulate various physiological processes. The molecular mechanism of the perception of BRs by the ectodomain of BRI1 remains not fully understood. It also remains elusive why a substantial difference in biological activity exists between the BRs. In this work, we study the binding mechanisms of the two most bioactive BRs, brassinolide (BLD) and castasterone (CAT), using molecular dynamics simulations. We report free-energy landscapes of the binding processes of both ligands, as well as detailed ligand binding pathways. Our results suggest that CAT has a lower binding affinity compared to BLD due to its inability to form hydrogen-bonding interactions with a tyrosine residue in the island domain of BRI1. We uncover a conserved nonproductive binding state for both BLD and CAT, which is more stable for CAT and may further contribute to the bioactivity difference. Finally, we validate past observations about the conformational restructuring and ordering of the island domain upon BLD binding. Overall, this study provides new insights into the fundamental mechanism of the perception of the two most bioactive BRs, which may create new avenues for genetic and agrochemical control of their signaling cascade.
Subject(s)
Arabidopsis Proteins/metabolism , Brassinosteroids/metabolism , Cholestanols/metabolism , Protein Kinases/metabolism , Steroids, Heterocyclic/metabolism , Arabidopsis/chemistry , Arabidopsis Proteins/chemistry , Brassinosteroids/chemistry , Cholestanols/chemistry , Hydrogen Bonding , Ligands , Models, Chemical , Molecular Dynamics Simulation , Protein Binding , Protein Conformation , Protein Kinases/chemistry , Steroids, Heterocyclic/chemistry , Thermodynamics , Tyrosine/chemistryABSTRACT
We report the results of atomistic molecular dynamics simulations on polymerized 1-butyl-3-vinylimidazolium-hexafluorophosphate ionic liquids, studying the influence of the polymer molecular weight on the ion mobilities and the mechanisms underlying ion transport, including ion-association dynamics, ion hopping, and ion-polymer coordinations. With an increase in polymer molecular weight, the diffusivity of the hexafluorophosphate (PF6-) counterion decreases and plateaus above seven repeat units. The diffusivity is seen to correlate well with the ion-association structural relaxation time for pure ionic liquids, but becomes more correlated with ion-association lifetimes for larger molecular weight polymers. By analyzing the diffusivity of ions based on coordination structure, we unearth a transport mechanism in which the PF6- moves by "climbing the ladder" while associated with four polymeric cations from two different polymers.
