Modeling and docking studies on novel mutants (K71L and T204V) of the ATPase domain of human heat shock 70 kDa protein 1.
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.
Faculty of Bioscience and Medical Engineering, Universiti Teknologi Malaysia, Skudai, Johor 81310, Malaysia. asitaelengoe@yahoo.com.
Asita
A
Elengoe
Faculty of Bioscience and Medical Engineering, Universiti Teknologi Malaysia, Skudai, Johor 81310, Malaysia. abunaser@fbb.utm.my.
Mohammed Abu
MA
Naser
Faculty of Bioscience and Medical Engineering, Universiti Teknologi Malaysia, Skudai, Johor 81310, Malaysia. saleh65@utm.my.
Salehhuddin
S
Hamdan
D019943:Amino Acid Substitution; D020134:Catalytic Domain; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D012984:Software; D013816:Thermodynamics
D018840:HSP70 Heat-Shock Proteins