A comprehensive study of HSA interaction with TMP using molecular docking and molecular dynamics methods: as an appropriate tool for drug delivery systems

Background: Human serum albumin (HSA) is one of the most prominent protein in human blood. Trimethoprim (TMP) is an efficient antibiotic drug for treatment of pneumocystis pneumonia (PCP). Patients with HIV/AIDS and cancer are extremely affected by the disease due to immune system deficiency. Objective: The aim of this study is to evaluate the molecular dynamics simulation (MD) of HSA with TMP for drug delivery systems. Materials and methods: In the first step, the 3D structure of HSA and TMP were provided by PDB and PubChem respectively. Then, the molecular docking was done via AutoDock Vina software and the best complex was selected due to the lowest binding energy. Finally, the structural characteristics of the above complex was evaluated. Results: The results showed that TMP binds to the HSA molecule with a binding energy of -7.3 kcal/mol and this binding causes changes in third and second structure of the HSA. Thus, the RMSD and RG results proved the third structural changes and the results obtained from DSSP confirmed the second structural modifications. The TMP-HSA complex formation accompanied with hydrophobic interaction between residues; Tyr150 and Ala291, His288, Leu238, Leu219, Lys199, Lys195, Glu153 and TMP. The TMP molecule had two hydrogen bond with Arg222 residue and three with Ser192. Furthermore, the final PDB file of the MD simulation process showed that the TMP molecule had reaction HSA (IIA chain). Conclusion: Due to the extensive application of TMP in infectious disease and appropriate interaction with HSA, the complex could be used for targeted transport of nanoparticles in the future.