Design of novel peptides to assess the inhibitory effect of Hsp90 alpha: An in silico approach

In the present investigation, protein-protein interaction studies were done between Hsp90 alpha, its co-chaperones and client proteins. Results showed that complex formation is important for stabilization and maturation of client proteins. Hsp organizing protein also known as HOP brings together Hsp90 alpha and Hsp70 and therefore, inhibiting Hsp90 alpha and HOP interaction may lead to the disruption of Hsp90 alpha-Hsp70 complex formation and thus destabilize and degrade the client proteins including p53. In order to inhibit Hsp90 alpha and HOP interaction, ten numbers of peptides have been designed considering those residues involved in the interaction between Hsp90 alpha and HOP using computational methods. In-silico docking method Hex 6.1 was used to assess the binding energy between peptides and Hsp90 alpha. Based on the energy values we selected the peptide with highest negative energy that was the indicative of most stable interaction. As peptides commonly form aggregates, amyloidogenic properties of the selected peptide were predicted and the peptide was accordingly modified. When the modified peptide was interacted with Hsp90 alpha, docking results showed peptide INSAYKLKYARG binds with Hsp90 alpha with highest negative free energy of -861.81kcal/mole. The docking of the complex with HOP showed less affinity than Hsp90 alpha alone showing the conformational changes upon inhibition