Molecular dynamics simulations of the cytolytic toxin Cyt1A in solution

Cytolytic toxin Cyt1A from Bacillus thuringiensis var. israelensis is used as an environmentally friendly insecticide, but its mode of action has not been clearly established. One main obstacle seems to be the lack of the experimentally determined structure of the toxin. As a first step in computer simulations of Cyt1A, in this paper, a three-dimensional molecular structure of Cyt1A in solution was generated by homology modeling, potential energy minimization and molecular dynamics. Regions of the toxin molecule that manifest increased conformational flexibility--and thus are likely to participate in the initial membrane binding and conformational changes--were then identified. Finally, the simulated structure was used to study the effect of a single amino-acid mutation that is known to abrogate the toxicity of Cyt1A in vivo.