Combined molecular docking and molecular dynamicssimulationto investigation of aflatoxin B1interaction with human serum albumin

Aflatoxin, a group of toxic fungal metabolites, is called Mycotoxin and is produced by a mildew called Asparicillus, which grows on some foods and can cause Aflatoxicosis in humananddomestic animals. aflatoxins are species B1, B2, G1, G2, M1 and M2. B1 is more abundant than others and its toxicity is higher than other types. These compounds are more important than other fungal toxins due to the effects ofcancer and acute poisoning [1]. These compounds, after entering the human body, can be linked to proteins in the bloodstream and distributed throughout the body. One of the most important of these proteins is human serum albumin (HSA).HSA is the major soluble protein constituents of the circulatory system and has many physiological functions.Its principal function is that it involves the binding, transport, and delivery of numerous drugs to their target organs. One of the most important factors affectingthe distribution and the free, active concentration of many drugs is binding affinity for HSA [2].One way of investigation these interactions is to use computational techniques such as molecular dynamics simulation and molecular docking. The combination of the two techniques in a protocol where docking is used for the fast screening of large libraries and MD simulations are then applied to explore conformations of the protein receptor, optimize the structures of the final complexes, and calculate accurateenergies, is a logical approach to improving the drug-design process and investigate these types of interactions[3]. In this study, AutoDock 4.2were used to determine the binding site and free energyof bindingof aflatoxinto human serum albumin. Then the conformation with the lowest binding energy was chosen from the mostpopulated cluster and the corresponding ligand-protein complex was used for further MD studies. The MD simulations were performed with GROMACS 5.4.1 software package, employing the CHARMM27 force field.The results showed that the free energy of binding of the high affinity site on HSA for Aflatoxin B1 was -8.58 kcal/mol and binding site was determined in domin I (in subdomain IB).The final structure of the complex was obtained and the RMSD value between it and the initialstructure of complex wasdetermined 0.33 Angstrom.The use combined Docking and MD Simulation can provide appropriate results for investigating the interactions of the ligand-protein.