Abstract
Abstract
Background
The pink bollworm (
Pectinophora gossypiella
) is one of the most destructive pests of cotton worldwide, causing substantial yield losses and economic damage. The deployment of Bt cotton expressing insecticidal proteins from
Bacillus thuringiensis
(Bt), including Cry1Ac in Bollgard I (BG-I) and Cry1Ac plus Cry2Ab in Bollgard II (BG-II), initially provided effective control of this pest. However, the evolution of resistance to both Cry1Ac and Cry2Ab has significantly reduced the effectiveness of Bt cotton. Previous studies have implicated ATP-binding cassette (ABC) transporters and mutant cadherin proteins as key factors mediating resistance through altered Bt toxin interactions and detoxification mechanisms. Although resistance mechanisms involving cadherin and ABC transporters have been reported, the comparative structural interactions of Cry1Ac, Cry2Ab, and Cry2Ad with these receptor proteins remain poorly understood in the pink bollworm. This study, therefore, aimed to investigate the molecular interactions of Cry1Ac, Cry2Ab, and Cry2Ad with pink bollworm mutant cadherin (PgMutCad) and ATP-binding cassette transporter (PgABC) using computational modeling, molecular docking, and molecular dynamics simulations.
Results
Protein structures were generated using homology modeling and ab initio prediction, depending on sequence variation and structural homology. Molecular docking and simulation analyses revealed distinct interaction patterns among the Cry proteins and resistance-associated targets. Among the toxins evaluated, Cry2Ab and Cry2Ad exhibited stronger binding affinities, structural stability, more favorable binding energetics, and persistent hydrogen-bond interactions with both PgMutCad and PgABC. These toxin-receptor complexes maintained compact conformations throughout the simulations, indicating stable and robust interactions. In contrast, Cry1Ac showed comparatively weaker interactions with the resistance-associated proteins.
Conclusion
The study provides new insights into the molecular basis of pink bollworm resistance to Bt toxins and highlights the critical role of mutant cadherin and ABC transporter proteins in this process. The strong and stable interactions observed for Cry2Ab and Cry2Ad suggest that these toxin variants represent promising candidates for the development of next-generation Bt cotton and improved pest management strategies. Although these findings are based on computational analyses and require experimental validation, they provide a structural framework for the rational design of novel Bt toxins and resistance-management approaches aimed at sustaining the long-term effectiveness of transgenic cotton against the pink bollworm.