Jornal de Bioinformática Aplicada e Biologia Computacional

In silico Binding Affinity Studies of Antipsychotic Drugs with Protein Phosphatases by Molecular Docking

Devaraju KS* , Sarojini R Bulbule and P Aravind

Background: In eukaryotic cells, protein phosphatases have grown to be the biggest family of signaling proteins and are essential enzymes that are involved in many facets of cellular regulation. With the exception of PP1 and PP2B, PPs have not received as much research attention as kinases have. Different protein phosphatases have been targeted in clinical studies using recent meta-analyses of antipsychotic medication efficacy and tolerability. The negative effects of current standard and atypical antipsychotic medications outweigh their therapeutic benefits. Therefore, it is necessary to review their binding activity with various protein phosphatases. As a result, the current study illustrates how various phosphatases respond to the antipsychotic medications such as Clozapine, Olanzapine, and Trifluoperazine.

Method: Utilizing Maestro 9.3, three commonly used antipsychotic medications are chosen to assess the likelihood of interactions with various PPs (schrodinger). The three antipsychotic medications were filtered using Lipinski's rule (ro5) prior to docking, and these compounds were also submitted to ADME-T characteristics to look at binding interactions. The antipsychotic medications with phenothiazine groups were used in the current study due to their potential interactions with various protein phosphatases. As a result, molecular docking was used to examine the binding potential of three commonly prescribed antipsychotic medications with various protein phosphatases.

Results: The results of docking score of antipsychotic drugs with six different PP’s ranges from -7.43 kJ mol^-1 to -2.91 kJ mol^-1. Among all the compounds, second generation drug Olanzapine showed the highest binding affinity of -7.43 kJ mol⁻¹ with PP5 when compared to other drugs.

Conclusion: Therefore, this study suggests that the Olanzapine has a greater affinity and exhibit non-specific modulatory effect on PP’s that need to be explored at biochemical and cellular level.