Shanthappa Pallavi M, Gowtham H G, Sridhara Setty Poojitha B, Alhewairini Saleh S, Barasarathi Jayanthi, Singh Pallavi, Murali M, Sayyed Riyaz, Kollur Shiva Prasad
School of Computing, Amrita Vishwa Vidyapeetham, Mysuru Campus, Mysuru, 570026, Karnataka, India.
Department of Studies and Research in Food Science and Nutrition, KSOU, Mysuru, 570006, India.
Sci Rep. 2025 Jul 1;15(1):20999. doi: 10.1038/s41598-025-07113-3.
Abscisic acid (ABA) agonists bind to the same receptors as ABA in plant cells and exhibit similar physiological effects. Even though synthetic ABA agonists like Pyrabactin, Quinabactin, Cyanabactin, and Opabactin can bind to the PYR1 receptor, no plant-derived natural ABA agonists have been reported. The present study explored the highly potent natural ABA agonists through the target inhibition efficacy of phytochemicals from the different parts of the Ficus carica plant against the binding of pyrabactin resistance 1 (PYR1) receptor (PDB: 3K3K) using computational approaches. Molecular docking analysis confirmed that among the 99 phytochemicals, five phytochemicals, such as Chlorogenic acid, Rutin, Quercetin, Schaftoside, and Imperatorin, were potentially bound at the active binding site of the PYR1 receptor target with the best docking scores below - 8.0 kcal/mol compared to other compounds and positive control ABA. Further, the ABA showed a - 7.6 kcal/mol docking score against the PYR1 receptor. Based on the best docking scores, out of 99 phytochemicals, five lead phytochemicals (viz., Chlorogenic acid, Rutin, Quercetin, Schaftoside and Imperatorin) and positive control (ABA) were further subjected to molecular dynamics (MD) simulation, principal component analysis (PCA), free energy landscape (FEL)and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) analysis. The results have proved that Rutin and Schaftoside were found to form the energetically stable complex with the PYR1 receptor at both 300 K and 325 K. Moreover, the result of the MM/PBSA technique indicated that Rutin and Schaftoside bound PYR1 receptor complexes exhibited lower binding free energy compared to ABA at both 300 K and 325 K. Considering all the results, the study concluded that Rutin and Schaftoside phytochemicals can be highly potent natural ABA agonists with considerable efficacy in binding to the PYR1 receptor active site. The study further needs the experimental validation of these phytochemicals (such as Rutin and Schaftoside) to understand their PYR1 receptor binding potential and for their use in sustainable agriculture.
脱落酸（ABA）激动剂在植物细胞中与ABA结合相同的受体，并表现出相似的生理效应。尽管像吡唑醚菌酯、喹菌酮、氰菌酮和邻苯二甲酰亚胺等合成ABA激动剂可以与PYR1受体结合，但尚未有植物来源的天然ABA激动剂的报道。本研究通过计算方法，利用无花果植物不同部位的植物化学物质对吡唑醚菌酯抗性1（PYR1）受体（PDB：3K3K）结合的靶向抑制效果，探索了高效的天然ABA激动剂。分子对接分析证实，在99种植物化学物质中，绿原酸、芦丁、槲皮素、schaftoside和欧前胡素这五种植物化学物质可能与PYR1受体靶点的活性结合位点结合，与其他化合物和阳性对照ABA相比，其最佳对接分数低于-8.0千卡/摩尔。此外，ABA与PYR1受体的对接分数为-7.6千卡/摩尔。基于最佳对接分数，在99种植物化学物质中，五种先导植物化学物质（即绿原酸、芦丁、槲皮素、schaftoside和欧前胡素）和阳性对照（ABA）进一步进行了分子动力学（MD）模拟、主成分分析（PCA）、自由能景观（FEL）和分子力学/泊松-玻尔兹曼表面积（MM/PBSA）分析。结果证明，芦丁和schaftoside在300K和325K时均与PYR1受体形成能量稳定的复合物。此外，MM/PBSA技术的结果表明，在300K和325K时，芦丁和schaftoside结合PYR1受体复合物的结合自由能均低于ABA。综合所有结果，该研究得出结论，芦丁和schaftoside植物化学物质可能是高效的天然ABA激动剂，在与PYR1受体活性位点结合方面具有相当的功效。该研究还需要对这些植物化学物质（如芦丁和schaftoside）进行实验验证，以了解它们与PYR1受体的结合潜力及其在可持续农业中的应用。
