The Role of Electrostatic Interaction to the Structural Stability of Nucleic Acid and Peptide
Dr. Zuojun Guo
Genomics Institute of the Novartis Resesearch Foundation
The closely placed phosphate charges along the charged biopolymer DNA backbone leads to strong electrostatic repulsion. However, when the DNA is immersed in an aqueous solution containing monovalent or divalent cations from added salts, the free energy of the system is lowered when counterions from the bulk condense on the backbone of the DNA. According to counterion condensation theory, each phosphate charge is reduced by the factor z theta, where theta is the number counterions associated per phosphate charge, z is the valence of counterions. Brownian Dynamics simulations also can be used to quantitatively describe condensation of monovalent and multivalent ions (from added salt) on the backbone of DNA.
The tumor suppressor gene p53 is responsible for maintaining the integrity of the human genome and plays a vital role in DNA repairing machinery. Loss of p53 tumor suppressor activity is a frequent defect in ~ 50% of human cancers. MDM2 controls the stability of p53 through ubiquitation to target the tumor suppressor protein for degradation by the proteasome. Inhibition the interactions between p53 and the E3 ubiquitin ligase MDM2/MDMX will reactivate the p53 pathway and selectively kill tumor cells. Extensive molecular dynamics simulations were used to study hydrocarbon linker stapled alpha-helical peptides which could be potential inhibitors of p53 peptide and MDM2.