Molecular docking of host-derived small molecules against pathogen effectors for novel drug leads in a plant disease complex

The continued threat of fungicide resistance development and new plant disease epidemics makes the quest for novel chemicals  a central theme in chemical crop protection. This study harnesses molecular docking tools to identify plant molecules that bind to pathogen effectors for pathogen control. Using the bacterial spot of tomato and pepper disease complex system, the docking of host-derived small molecules was evaluated against pathogen effectors. The 3D SDF format of candidate small molecule ligands from tomato and pepper  were used for docking analyses against 11 T3SS effectors found in all four bacterial spot species. Effector protein structure was  sourced from protein data bank where available, otherwise, the protein sequence of each effector was used for homology modeling using Swiss-Model. In total, 310  small molecules from tomato and pepper were docked against the effectors. An adapted ADME/T analysis assessed their pharmacokinetic properties and toxicity profiles. Docking simulations identified 56 ligands with good binding scores and ADME/T analysis identified eight candidates that complied with Lipinski’s Rule of Five and exhibited favorable pharmacokinetics, making them potential candidates for use in targeted disease control. This study provides a framework for identifying host-derived small molecules that dock to pathogen effectors, providing baseline for  their potential deployment as candidates for  disease control.
Keywords: Plant disease management, Xanthomonas species, Host-derived bioproducts, Molecular docking, ADME analysis, Sustainable agriculture.