title: Aromatic-aromatic interactions in the formation of the MDM2-p53 complex.
abstract: Although the molecular interaction of MDM2 with the transactivation domain of p53 has been thoroughly studied, there is very limited information regarding the steps involved in the recognition mechanism between these proteins. On this basis, we performed four high-temperature molecular dynamics simulations in explicit solvent to gain insight into the interactions involved in the fist contact toward the formation of the complex. We found that the presence of specific intermolecular aromatic pairs at the interface of the complex, around the native-like state of MDM2, is consistent among independent molecular dynamics runs. This observation suggests that aromatic-aromatic interactions are closely related to the first contact between MDM2 and p53. Thus, we propose that aromatic-aromatic interactions are an important, and probably essential, requirement for the formation and stabilization of the MDM2-p53 complex.
authors: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 321 Church Street SE, Minneapolis, MN 55455, USA. mef@ddt.biochem.umn.edu
authors: L Michel
authors: LM
authors: Espinoza-Fonseca
authors: Jazmín
authors: J
authors: García-Machorro
mesh_terms: D024322:Amino Acids, Aromatic / Q000737:chemistry*; D000818:Animals; D006358:Hot Temperature; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry*; D013696:Temperature; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*; D029867:Xenopus Proteins / Q000737:chemistry
chemical_list: D024322:Amino Acids, Aromatic; D016159:Tumor Suppressor Protein p53; D029867:Xenopus Proteins; D051736:Proto-Oncogene Proteins c-mdm2