Quantum chemistry calculations at the levels of MP2/cc-pVDZ and MP2/cc-PVTZ have been carried out to study residue-specific interactions at the hydrophobic p53-MDM2 binding interface. The result of the calculation, based on structures from nanosecond molecular dynamics simulation, revealed that 19Phe, 22Leu, and 23Trp of p53 have the strongest binding interaction with MDM2 followed by 26Leu and 27PrO. The specific residues of MDM2 that have dominant binding interactions with p53 are specifically identified to be 51Lys, 54Leu, 62Met, 67Tyr, 72GIn, 94Lys, 96His, and 100Tyr. The p53-MDM2 binding interaction is dominated by van der Waals interaction and to a lesser degree by electrostatic interaction. The MP2 results are in generally good agreement with those from the force field calculation while the DFT/B3LYP calculation failed to give attractive interaction energies for certain residue-residue interactions due to the lack of dispersion energy.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Surfaces, Coatings and Films
- Materials Chemistry