Molecular Docking Analysis of GSTP1 Variants with Paclitaxel and JNK: Exploring Chemoresistance and Detoxification in Cancer

Abstract

GSTP1 I105V polymorphism's impact on detoxification of paclitaxel and chemoresistance is studied through molecular docking and computational modelling. The interactions between Isoleucine (Ile105) and Paclitaxel showed a higher binding affinity than that of the Valine (Val105) variant, leading to higher enzymatic activity and decreased intracellular drug levels. Furthermore, docking simulations with glutathione (GSH) revealed similar interactions levels between the two variants. Also, protein-protein docking of GSTP1 with the JNK signaling protein with ClusPro, HDOCK, and HADDOCK servers, indicated negligible binding differences between variants. The findings can hint how GSTP1 polymorphisms can potentially play a role in changing the levels of hematological and neurological toxicities during paclitaxel chemotherapy. These results highlight the relevance of GSTP1 genotyping in chemotherapy dosage optimization and dose delay.