Revista de bioinformática aplicada y biología computacional

Does Protein Kinases exhibit Binding Affinity with Antipsychotic Drugs? – A Molecular Docking Approach

Kiran.P.C1 , Sarojini.R.Bulbule1 , Ramesha Hanumanthappa1 , Hemalatha Nanjaiah2 , and Devaraju K S1

Introduction: Antipsychotic drugs are used to treat psychosis and majorly used are phenothiazine drugs like Clozapine, Olanzapine, and Trifluoperazine. Both typical and atypical antipsychotic drugs are known to bind serotonin, dopamine, histamine, muscarine receptors and other associated proteins. However, it is not known that these antipsychotic drugs would bind to kinases are not. Kinases have emerged as the largest family of signaling proteins in eukaryotic cells and are involved in every aspect of cellular regulation. All these antipsychotic drugs crossing plasma membrane and found to be in cytosol have all the possibility of interacting with the other molecules. On the other hand all antipsychotic drugs without an exception they exhibit side effects as Food and Drug Administration (FDA) approved drowsiness, dizziness, restlessness, weight gain so on.

Method: The current study is carried out to know whether these antipsychotic drugs bind to different various protein kinases or not, this was done by using Molecular docking analyses which were performed using PyMol, Discovery Studio Biovia 2017, AutoDock Vina, AutoDock Tools version 1.5.4 and LigPlot to evaluate their binding free energy (ΔG).

Results: Among all the compounds, Trifluoperazine exhibited the higher binding affinity of – 9.1 Kcal mol^-1 with Casein kinase 1 when compared to Clozapine and Olanzapine.

Conclusion: Further his study suggests that the Trifluoperazine exhibits a non-specific modulatory effect on kinases in general, Casein kinase I in particular. This need to be further explored In Vitro and molecular level studies.