Molecular docking study of the carbamazepine and lamotrigine interaction with peroxidase

Background and Aim : One of the side effects of antiepileptic drugs is the increased production of reactive species in patients. Due to the involvement of the peroxidase enzyme in reducing oxidative stress, this study aimed to investigate the molecular interaction of carbamazepine and lamotrigine with this enzyme by molecular docking technique.Methods : The crystal structure of HRP was obtained from Protein Data Bank (Id:1hch) and the 3D coordination of drugs were obtained from Pub Chem. Molecular docking simulations were performed using auto dock 4.0 software. Lamarckian genetic algorithm with GA population size 100 was selected. The lowest energy conformation with the largest cluster of every docking simulation were extracted and analyzed.Results : Autodock Vina results showed that both carbamazepine and lamotrigine were located between helix F and B (distal domain). However, furder studies by Autodock 4.0 indicated that carbamazepine preferentially binds to helix F (amino acids 163-170) it has a weaker binding to helix B. Whereas lamotrigine makes better connections with Arg38 and His42 of helix B than helix F.The results suggested that both drugs could interact with peroxidase using hydrophobic and interactions and hydrogen bonds.Conclusion : Both drugs bind to the distal domains of the enzyme. Since helix B is the catalytic subdomain of peroxidase, it seems that Lamotrigine further altered the structure of the active site than carbamazepine.

کلیدواژه ها:

carbamazepine ، lamotrigine ، peroxidase ، molecular docking