In silico Screening of Potential Bioactive Compounds for the Development of New Pest-control Strategies against Migratory Locusts

Abstract

Agriculture is imperative to Pakistan’s economy, and pest attacks can greatly undermine the potential of the sector. Locust attacks are on the rise and not all farmers are well equipped to timely and effectively get such attacks under control. Odorant-binding proteins play a key role in the locusts' olfactory perception system. Despite there being dozens of OBPs, not many have their crystal structures determined. This study aimed to generate in silico models of the known OBPs of Locusta migratoria, and perform a screening of bioactive ligands against the OBPs to identify potential compounds which have a high binding affinity for the OBPs. The compounds with high affinities can then eventually be used to develop biological controls or traps for the locusts. We carried out ab initio modeling of 4 OBPs. The highest quality models were prepared for docking with our selected ligands. OBP1, the only protein which had its crystal structure resolved already, showed a greater binding affinity for all the compounds being tested compared to its in silico predicted counterparts. We visualized our docked molecules and analyzed the residues involved in high-affinity binding for the four compounds that showed the greatest binding affinity of all: Phenobarbital, Phenobarbital D-5, Cyclobarbital M, and Babriphenyl D-5. One of the most promising findings of our project was the discovery that phenobarbital binds to our modeled odorant-binding proteins with a high affinity. Phenobarbital is known to enhance the rate of moulting in locusts, and we hypothesize that it can potentially serve as an olfactory attractant, however, that would need to be tested in vitro. Another interesting finding was that fact that Cyclobarbital M binds to the OBP1 exclusively using hydrogen bonding. This is very surprising given that our current understanding of OBPs suggests that they are not required for the transport of hydrophilic ligands. However, this finding suggests that perhaps OBPs may have more diverse role in odorant transfer than previously known.