Abstract
The purpose of exploring protein interactions between human adenovirus and heat shock protein 70 is to exploit a potentially synergistic interaction to enhance anti-tumoral efficacy and decrease toxicity in cancer treatment. However, the protein interaction of Hsp70 with E1A32 kDa of human adenovirus serotype 5 remains to be elucidated. In this study, two residues of ATPase domain of human heat shock 70 kDa protein 1 (PDB: 1 HJO) were mutated. 3D mutant models (K71L and T204V) using PyMol software were then constructed. The structures were evaluated by PROCHECK, ProQ, ERRAT, Verify 3D and ProSA modules. All evidence suggests that all protein models are acceptable and of good quality. The E1A32 kDa motif was retrieved from UniProt (P03255), as well as subjected to docking interaction with NBD, K71L and T204V, using the Autodock 4.2 program. The best lowest binding energy value of −9.09 kcal/mol was selected for novel T204V. Moreover, the protein-ligand complex structures were validated by RMSD, RMSF, hydrogen bonds and salt bridge analysis. This revealed that the T204V-E1A32 kDa motif complex was the most stable among all three complex structures. This study provides information about the interaction between Hsp70 and the E1A32 kDa motif, which emphasizes future perspectives to design rational drugs and vaccines in cancer therapy.
Highlights
The current study explores the interaction between human heat shock protein 70 (Hsp70) and adenovirus
The results show that residues of the nucleotide binding domain (NBD) model in the most favorable region were more than 80% except K71L and T204V mutants which scored slightly less than 80% for the most favored region (Table 3)
We developed 3D mutant models (K71L and T204V), using NBD as a template
Summary
The current study explores the interaction between human heat shock protein 70 (Hsp70) and adenovirus. Despite the fact that hyperthermia in combination with adenoviral therapy has shown their effectiveness in vitro, currently no clinical trials for this combination treatment is underway These oncolytic adenoviruses are promising as anticancer agents, clinical experiences show that these agents alone failed to generate sustained clinical responses or to cause complete tumor regressions. The purpose of investigating the protein interaction between adenovirus and Hsp is to exploit a potentially synergistic interaction to enhance anti-tumoral efficacy and decrease toxicity in cancer therapy; but the molecular interaction between Hsp with E1A32 kDa of human adenovirus serotype 5 remains to be elucidated. K71 and T204 of ATPase domain of human heat shock 70 kDa protein 1 (PDB: 1 HJO) involved in playing a vital role in catalytic activity were mutated. The docking program (Autodock Version 4.2) has been used to predict the preferred sites of interaction between the NBD, K71L and T204V mutant models with E1A32 kDa motif
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