Here we found three different hydrophobic patches present in Hsp90, each in N terminal, C terminal and middle domain. Hydrophobic patches and its location in Hsp90 co-chaperones were also predicted [Table 2]. Here we considered a cut-off value of the interaction of Hsp90 (predicted hydrophobic patches) and its co-chaperones binding site on the Hsp90 protein percentage similarity was 40%. Based on our assumption we have identified a hydrophobic patch “TFSCLG” located in N terminal domain of p23 which interact to N terminal domain of Hsp90

and the value of percentage similarity was 42.86 [Table 3]. Similarly we have observed that in the N terminal domain (1–153) of Aha1, a hydrophobic patch “VEISVSL” was identified with a percentage similarity value of 42.86 which interacted to the middle domain of Hsp90. A hydrophobic patch “VMQFIL” having a percent similarity of 57.14 was identified in the C terminal domain Selleckchem Alpelisib (138–378) of Cdc37 and this patch was responsible to interact with N terminal domain of Hsp90 [Table 4]. We have considered a cut-off value of the interaction

of Hsp90 (predicted hydrophobic patches) and its kinases binding site on the Hsp90 protein to be 40% similarity. Based on our assumption we have identified Aurora Kinase inhibitor kinase Ask1, C-Raf,Raf-1 having a hydrophobic patch “VQVVLFG” (C terminal domain), “FGIVLY” (C terminal domain), “YGIVLYE” (C terminal domain) respectively which interact to middle domain of Hsp90 and the value of maximum % similarity was 71.43. Similarly, We have observed other kinase protein like Akt, Cdk2, ErbB2 which interact to middle domain of Hsp90 and the value of percentage until similarity was 50%. Protein–protein docking results obtained through Cluspro 2.0 server showing that MODEL 5 (Multichaperone complex + mutant p53) best represents the association of Hsp90 with mutant p53 and helping its stabilization in tumor cells [Fig. 4]. Strong interaction between

Multichaperone complex Hsp90 and mutant p53 as shown by protein–protein prediction server (Cluspro 2.0). Here a Multichaperone complex of Hsp90 was generated by docking it to its partner chaperone Hsp70 and co-chaperones like Aha1 and Hsp40 which gave a favourable complex with docking energy of −711 kcal/mol [Table 6]. The result suggests that Hsp90 in association with its partner chaperone (Hsp70) and co-chaperones (Hsp40 and Aha1) forms stable multichaperone complex which favors strong interaction with mutant p53 (Docking energy = −1103.9 kcal/mol) as compared to wild type p53 [Table 5] (Docking energy = −894.6 kcal/mol) as determined by protein–protein docking through Cluspro 2.0 server [Fig. 5]. This strong interaction leads to stabilization of mutant p53 and prevents it from being degraded via ubiquitin-mediated proteasomal degradation. Molecular docking has been carried out using Molegro Virtual Docker.