Understanding the binding interaction in therapeutic prevention of inflammation by controlling Hsp90 through curcumin and epigallocatechin

Abstract

Inflammatory checkpoint blockade is the trend of current research targeting Hsp90 with either phytochemical or commercial drugs. It has been extensively studied globally by researchers but nevertheless has been unable to prevent inflammatory disorders successfully. These key considerations set the stage for identification of different combinatorial strategies, curcumin and epigallocatechin to target Hsp90 involved in inflammatory disorders to gain insight into the benefits of this approach. The primary objective in present study is the prior prediction of the binding interactions of curcumin and epigallocatechin with Hsp90 in the living system through computational studies. A suitable animal model sequence for Hsp90 studies was fetched through PHYLOGENY and BLAST. Hsp90 Mus musculus was obtained as a homologous sequence to Hsp90 Homo sapiens and its tertiary structure was homology modeled as its unabridged experimentally derived structure was not available. In additional tertiary model structure was verified using different tools. Single ligand docking and multiple ligand simultaneous docking of curcumin and epigallocatechin to the modeled Hsp90 structure was carried out using the AutoDock tool. In single ligand docking, curcumin had the binding affinity of − 8.3 kcal/mol, while for epigallocatechin − 5.9 kcal/mol and the multiple ligand simultaneous docking binding affinity for Hsp90 to curcumin and epigallocatechin was − 8.4 kcal/mol. Their interface residues were explored for mutational studies and were found to be in an unstabilized state, possibly corresponding to the conformational changes in Hsp90. These strategies emphasize the rationale for combining the modalities, curcumin and epigallocatechin in the successful reduction of Hsp90 expression, henceforth the inflammatory checkpoint would be controlled to augment the anti-inflammatory response.