STRUCTURE-BASED DISCOVERY OF ABSCISIC ACID RECEPTOR AGONISTS TARGETING ZMPYL9 AND ZMPYL12 FOR AGROCHEMICAL DEVELOPMENT

Abstract

Abiotic stress, particularly drought, remains a major limitation to crop productivity, necessitating innovative strategies to enhance plant resilience. Abscisic acid (ABA) signalling, mediated by PYR/PYL/RCAR receptors, plays a central role in stress adaptation; however, structural and functional insights into specific maize receptors such as ZmPYL9 and ZmPYL12 remain limited. This study employed an integrated computational approach to characterize these receptors and identify potential ABA-mimicking agrochemicals. High-quality homology models of ZmPYL9 and ZmPYL12 were constructed using templates with >94% sequence identity, yielding structurally robust models validated by stereochemical and non-bonded interaction metrics. Pharmacophore modelling and molecular docking revealed key ligand-binding features consistent with the canonical gate-latch-lock activation mechanism. Several compounds exhibited strong binding affinities (≤ −10 kcal/mol), while MM-GBSA analysis identified compounds 10661840 (−96.18 kcal/mol) and 10588337 (−93.21 kcal/mol) as the most stable ligands for ZmPYL9, and compound 134611692 (−94.73 kcal/mol) for ZmPYL12. Drug-likeness evaluation confirmed compliance with agrochemical criteria, while ADMET profiling indicated high bioavailability, low metabolic interference, and minimal toxicity. Notably, ZmPYL9 demonstrated superior ligand-binding performance, suggesting greater suitability for targeted modulation. This study therefore provide novel insights into receptor-specific ligand interactions and establishes a robust structure-based framework for the rational design of ABA agonists. The identified lead compounds represent promising candidates for developing environmentally safe agrochemicals aimed at improving crop tolerance to abiotic stress.Top of Form