title: Investigation of solvent effect and NMR shielding tensors of p53 tumor-suppressor gene in drug design.
abstract: The p53 tumor-suppressor gene encodes a nuclear phosphoprotein with cancer- inhibiting properties. The most probable cancerous mutations occur as point mutations in exons 5 up to 8 of p53, as a base pair substitution that encompasses CUA and GAT sequences. As DNA drug design represents a direct genetic treatment of cancer, in the research reported computational drug design was carried out to explore, at the Hartree-Fock level, effects of solvents on the thermochemical properties and nuclear magnetic resonance (NMR) shielding tensors of some atoms of CUA involved in the hydrogen-bonding network. The observed NMR shielding variations of the solutes caused by solvent change seemed significant and were attributed to solvent polarity, and solute-solvent and solvent-solute hydrogen-bonding interactions. The results provide a reliable insight into the nature of mutation processes. However, to improve our knowledge of the hydration pattern more rigorous computations of the hydrated complexes are needed.
authors.affiliation: Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. shi_irani@yahoo.com
authors.forename: S
authors.initials: S
authors.lastname: Irani
authors.forename: M
authors.initials: M
authors.lastname: Monajjemi
authors.forename: B
authors.initials: B
authors.lastname: Honarparvar
authors.forename: Sm
authors.initials: S
authors.lastname: Atyabi
authors.forename: M
authors.initials: M
authors.lastname: Sadeghizadeh
mesh_terms: D001483:Base Sequence; D055598:Chemical Phenomena; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D015195:Drug Design; D016158:Genes, p53; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D050997:Nanomedicine; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics; D017354:Point Mutation; D012997:Solvents; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D012997:Solvents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53