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 selleck (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 find protocol 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 Dichloromethane dehalogenase 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.