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.