title: In Silico Molecular Modeling and Docking Studies on Novel Mutants (E229V, H225P and D230C) of the Nucleotide-Binding Domain of Homo sapiens Hsp70.
abstract: In this study, we explored the possibility of determining the synergistic interactions between nucleotide-binding domain (NBD) of Homo sapiens heat-shock 70 kDa protein (Hsp70) and E1A 32 kDa of adenovirus serotype 5 motif (PNLVP) in the efficiency of killing of tumor cells in cancer treatment. At present, the protein interaction between NBD and PNLVP motif is still unknown, but believed to enhance the rate of virus replication in tumor cells. Three mutant models (E229V, H225P and D230C) were built and simulated, and their interactions with PNLVP motif were studied. The PNLVP motif showed the binding energy and intermolecular energy values with the novel E229V mutant at -7.32 and -11.2 kcal/mol. The E229V mutant had the highest number of hydrogen bonds (7). Based on the root mean square deviation, root mean square fluctuation, hydrogen bonds, salt bridge, secondary structure, surface-accessible solvent area, potential energy and distance matrices analyses, it was proved that the E229V had the strongest and most stable interaction with the PNLVP motif among all the four protein-ligand complex structures. The knowledge of this protein-ligand complex model would help in designing Hsp70 structure-based drug for cancer therapy.
authors: Department of Biosciences and Health Sciences, Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia, 81310, Skudai, Johor, Malaysia.
authors: Asita
authors: A
authors: Elengoe
authors: Department of Biosciences and Health Sciences, Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia, 81310, Skudai, Johor, Malaysia. saleh65@utm.my.
authors: Salehhuddin
authors: S
authors: Hamdan
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular
chemical_list: D018840:HSP70 Heat-Shock Proteins
keywords: Adenovirus; Binding energy; Hsp70; NBD; PNLVP motif; Stable