Computational techniques like molecular docking, molecular dynamic simulations, and binding free energy calculation have been successfully applied for molecular mechanism study. Although these techniques were applied primarily in drug design, they can also be applied to pesticide design due to the similarity between drug and pesticide. However, successful examples of computational mechanism study of pesticide have been comparatively rare.Gibberellins (GAs) are phytohormones essential for many developmental processes in plants (1). In this work, fundamental mechanism of hormone perception by receptor GID1 has been studied by performing computational simulations, revealing a new GA-binding channel of GID1 and a novel hormone perception mechanism involving only one conformational state of GID1 (Figure 1). The novel hormone perception mechanism demonstrated here is remarkably different from previously proposed/speculated mechanism involving two conformational states (�OPEN� and �CLOSED�) of GID1 (Figure 1)(2). According to the new hormone perception mechanism, GA acts as a �conformational stabilizer�, rather than the previously speculated �allosteric inducer�, to induce the recognition of protein DELLA by GID1 (3). The novel mechanistic insights obtained in this study provide a new starting point for further studies on the detailed molecular mechanisms of GID1 interacting with DELLA and various hormones and for mechanism-based rational design of novel, potent growth regulators that target crops and ornamental plants.References:Shimada A, Ueguchi-Tanaka M, Nakatsu T, Nakajima M, Naoe Y, Ohmiya H, Kato H, Matsuoka M. 2008. Structural basis for gibberellin recognition by its receptor GID1 Nature 456(27): 520-523Murase K, Hirano Y, Sun TP, Hakoshima T. 2008. Gibberellin-induced DELLA recognition by the gibberellin receptor GID1. Nature 456(27): 459-463Hao GF, Yang SG, Yang GF, Zhan CG. 2012. Computational Gibberellin-Binding Channel Discovery Unraveling the Unexpected Perception Mechanism of Hormone Signal by Gibberellin Receptor. J. Comput. Chem. 34(24): 2055-2064  Figure 1. Comparison between the previously and newly proposed perception mechanisms. (A  ) According to the previously proposed mechanism, the GA binding induces a conformational switch in the N-terminal region of GID1 between two states, i.e. the �OPEN� and �CLOSED� states. (B  ) According to the new mechanism proposed in this study, GA is perceived through a new channel and acts as a �conformational stabilizer� of GID1 to stimulate DELLA protein recognition.

Computational discovery of gibberellin-binding channel and perception mechanism

248th National Meeting (2014)

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