MOLECULAR DYNAMICS SIMULATION OF HOMOLOGY MODELED CYTOSOLIC Hsp90 ISOFORM FROM ARABIDOPSIS THALIANA

Heat-shock proteins (Hsps) are molecular chaperones regulating protein folding so as to ensure correct conformation, translocation and to avoid protein aggregation. Despite Hsps playing a cytoprotective role and protect the cells from adverse stressful stimuli, some of them such as Hsp90 are involved in the maturation and stabilization of a variety of oncogenic proteins which are critical for oncogenesis and malignant progression. Many oncogenic proteins responsible for the transformation of cells to cancerous forms are client proteins of Hsp90. Targeting Hsp90 with chemical inhibitors would degrade these oncogenic proteins, and thus serve as useful anticancer agents. Main focus of the present in silico investigation was to predict the 3D structure of seven different isoforms of Hsp90 of Arabidopsis thaliana, using molecular modelling techniques. Attempt was also made to dimerize Hsp90 and further dock this protein on to green tea flavonoid Epigallocatechin (EGC) followed by Molecular Dynamic (MD) simulation under explicit solvent conditions. The simulated docked complex was later analyzed for energy profile, root mean square deviation (RMSD), root mean square fluctuation (RMSF), polar contacts and salt bridge formation.