title: Quantum mechanical studies of residue-specific hydrophobic interactions in p53-MDM2 binding.
abstract: 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 (19)Phe, (22)Leu, and (23)Trp of p53 have the strongest binding interaction with MDM2 followed by (26)Leu and (27)Pro. The specific residues of MDM2 that have dominant binding interactions with p53 are specifically identified to be (51)Lys, (54)Leu, (62)Met, (67)Tyr, (72)Gln, (94)Lys, (96)His, and (100)Tyr. 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.
authors.affiliation: Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ding
authors.forename: Ye
authors.initials: Y
authors.lastname: Mei
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011485:Protein Binding; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D011789:Quantum Theory; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2