Molecular docking and molecular dynamics simulation study on the toxicity mechanism of bongkrekic acid

BKA belongs to gram-negative brevibacterium. It can cause poisoning in humans or animals and can be fatal in severe cases. There are few investigations on toxic mechanisms of BKA because of foodborne factors. MD simulations were used to study the stability and intermolecular interactions of BKA and ANT complexes to reveal the mechanism of BKA in this paper. BKA blocked ANT protein translocation mainly through Van der Waals force, hydrophobic and hydrogen bonding interactions by the MD simulations. The conformational flexibility of the complex system during different simulation times indicated that BKA affected the conformational changes of ANT through strong interactions of hydrogen bonds with active domain residues Gln-93, Tyr-196, Arg-287 and Arg-245. The results of binding free energy, principal component analysis, hydrophobic interactions and root-mean-square fluctuation showed that the prominent binding force of Tyr-196 with C26 of BKA was significant to the toxicity. The active site interactions analysis indicated that the essential positively charged polar amino acids which play a crucial role within the active site of the ANT protein undergo conformational changes with BKA as the branch point.