ABSTRACT
Computational and theoretical methods have recently played crucial parts in helping us to comprehend toxic mechanisms at the molecular level of two closely related dipteran-specific toxins: Cry4Aa and Cry4Ba. These mosquito-larvicidal proteins produced by Bacillus thuringiensis subsp. israelensis have been exploited as a safe bioinsecticide for controlling mosquitoes. We have been employing various computational techniques, such as protein-structure alignments, protein bioinformatics, homology-based modeling, protein–protein docking, and molecular dynamics (MD) simulations, to study Cry4Aa and Cry4Ba toxins. Nevertheless, if we desire to engineer these protein-based insecticides to be a better mosquito-active toxin, it is necessary to understand details of their 192toxic mechanisms. To this end, computational methods have been employed together with biochemical and biophysical experiments to explore structure–function relationships and dynamics of these two Cry toxins. Their structural basis of membrane-pore formation has allowed us to model and design further experimentation. Overall, this chapter provides the essential fundamentals of in silico techniques used to explore more insights into the Cry toxin-induced pore architecture and their applications for redesigning a better modified active toxin.
