title: Molecular dynamics-based identification of novel natural mortalin-p53 abrogators as anticancer agents.
abstract: BACKGROUND
  Cancer is one of the leading causes of mortality worldwide that requires attention in terms of extensive study and research. Eradication of mortalin-p53 interaction that leads to the inhibition of transcriptional activation or blocking of p53 from functioning as a suppressor and induction of nuclear translocation of p53 can prove to be one of the useful approaches for cancer management.
  
  
  RESULTS
  In this study, we used structure-based approach to target the p53-binding domain of mortalin in order to prevent mortalin-p53 complex formation. We screened compounds from ZINC database against the modeled mortalin protein using Glide virtual screening. The top two compounds, DTOM (ZINC 28639308) and TTOM (ZINC 38143676) with Glide score of -12.27 and -12.16, respectively, were identified with the potential to abrogate mortalin-p53 interaction. Finally, molecular dynamics simulations were used to analyze the dynamic stability of the ligand-bound complex and it was observed that residues Tyr196, Asn198, Val264 and Thr267 were involved in intermolecular interactions in both the simulated ligand-bound complexes, and thus, these residues may have a paramount role in stabilizing the binding of the ligands with the protein.
  
  
  CONCLUSIONS
  These detailed insights can further facilitate the development of potent inhibitors against mortalin-p53 complex.
authors.affiliation: a School of Biotechnology, Jawaharlal Nehru University , New Delhi , India and.
authors.forename: Neha
authors.initials: N
authors.lastname: Nagpal
authors.affiliation: a School of Biotechnology, Jawaharlal Nehru University , New Delhi , India and.
authors.forename: Sukriti
authors.initials: S
authors.lastname: Goyal
authors.affiliation: a School of Biotechnology, Jawaharlal Nehru University , New Delhi , India and.
authors.forename: Jaspreet Kaur
authors.initials: JK
authors.lastname: Dhanjal
authors.affiliation: b Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science & Technology (AIST) , Tsukuba , Ibaraki , Japan.
authors.forename: Liu
authors.initials: L
authors.lastname: Ye
authors.affiliation: b Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science & Technology (AIST) , Tsukuba , Ibaraki , Japan.
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.affiliation: b Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science & Technology (AIST) , Tsukuba , Ibaraki , Japan.
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.affiliation: a School of Biotechnology, Jawaharlal Nehru University , New Delhi , India and.
authors.forename: Rupesh
authors.initials: R
authors.lastname: Chaturvedi
authors.affiliation: a School of Biotechnology, Jawaharlal Nehru University , New Delhi , India and.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Grover
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D054852:Small Molecule Libraries / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D024101:Mitochondrial Proteins; D054852:Small Molecule Libraries; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Cancer; inhibitor; molecular dynamics; mortalin; natural; p53