Hsp90 is a molecular chaperone which is engaged in the repair of diverse oncogenic proteins.
Additionally, it is overexpressed in cancer cells along with co-chaperones, whereas normal cell Hsp90
(less than 2 % of cellular proteins) resides in an uncomplexed state. Hence, this chaperone is an encouraging
target for the discovery of novel chemical entities against cancer. Proteins execute their functions
by interacting with various macromolecules. The conformational flexibility of polypeptides helps them
to adopt a shape corresponding to their partner molecules. Hsp90 is a highly flexible polypeptide which
can accommodate a wide variety of dynamic states. The major cause for this structural dynamism is the
intrinsic flexibility of the protein. In this review, the structure and function of Hsp90 chaperone are discussed.
This is followed by a description of the factors regulating the proteins flexibility. Finally, dynamics
dependent drug designing strategy (induce fit docking and molecular dynamics simulation) for
the discovery of novel Hsp90 inhibitors is discussed.
Keywords: Cancer, Hsp90, intrinsic flexibility, dynamics regulation, drug design, induced fit docking,
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