• A Study of Cariprazine's effect on tau microtubule-associated protein (2MZ7) by molecular docking method
  • Aria Hajihassan,1,*
    1. Department of Microbiology, Medical branch, Islamic Azad University, Tehran, Iran


  • Introduction: Tau is considered one of the most significant proteins involved in binding and stabilizing microtubules, constituting over 80% of neuronal microtubule- associated proteins.1 As a result, tau’s mutation or hyperphosphorylation is highly involved in the development of different progressive neurodegenerative disorders like Alzheimer’s disease (Figure 1).2 As a new dopamine D2 receptor partial agonist, Cariprazine, has been investigated in a variety of psychiatric disorders, including schizophrenia, bipolar disorders, and major depressive disorder.3,4 Our purpose of this study was to determine whether this antipsychotic Drug can bind to the tau protein receptor as a ligand.
  • Methods: Through the docking strategy, which is an analytical descriptive technique, we first downloaded the 3D structure (Pdb) of the tau protein (267-312 nucleotides) from the UniProt site (Figure 2). Then, through the Chimera software (Version.1.17.1), we made the required adjustments such as removing solvents, evacuating water molecules, adding flux, etc. In the following step, we downloaded the 3D structure of Cariprazine (427.4 g/mol) from the PubChem site (Figure 3). In addition, we selected the appropriate grade box by using a molecular spatial analysis, performed by Deepsite (Vina data/ X=16:2092, Y= -6.1601, Z= -20.9144). Drug and protein were placed as ligand and receptor in PyRx software (Version.0.8). Both Data were selected separately and the docking process started. The Data output was checked as an Excel file.
  • Results: According to the docking process, the results were as follows. (Table 1.) LIGAND BINDING AFFINITY RMSD/UB RMSD/LB FINALPRP_11154555_UFF_E=451.93 -5.4 0 0 FINALPRP_11154555_UFF_E=451.93 -5.3 3.187 2.375 FINALPRP_11154555_UFF_E=451.93 -5.2 9.298 5.019 FINALPRP_11154555_UFF_E=451.93 -5.2 4.504 2.842 FINALPRP_11154555_UFF_E=451.93 -5.2 9.085 4.521 FINALPRP_11154555_UFF_E=451.93 -5.2 5.247 2.852 FINALPRP_11154555_UFF_E=451.93 -5.1 1.989 1.401 FINALPRP_11154555_UFF_E=451.93 -5 12.391 8.372 FINALPRP_11154555_UFF_E=451.93 -5 12.48 7.937 Table 1. Vina Wizzard’s Data indicating Cariprazine-Tau’s binding affinity and rmsd
  • Conclusion: Tau is one of the key proteins in Alzheimer’s disease, on which many studies are conducted. As claimed by Docking results, we found that there is a probability of binding Cariprazine to the tau protein, therefore the clinical trial period of this drug can begin in the field of Alzheimer’s disease.
  • Keywords: Keywords: tau microtubule-associated protein, Cariprazine, Docking method, Alzheimer’s disease