title: Molecular dynamics studies on Mdm2 complexes: an analysis of the inhibitor influence.
abstract: p53 is a powerful anti-tumoral molecule frequently inactivated by mutations or deletions in cancer. However, half of all human tumors expresses wild-type p53, and its activation, by antagonizing its negative regulator Mdm2, might offer a new strategy for therapeutic protocol. In this work, we present a molecular dynamics study on Mdm2 structure bound to two different known inhibitors with the aim to investigate the structural transitions between apo-Mdm2 and Mdm2-inhibitor complexes. We tried to gain information about conformational changes binding a benzodiazepine derivative inhibitor with respect the known nutlin and the apo form. The conformational changes alter the size of the cleft and were mainly in the linker regions, suggesting that the overall dynamic nature of Mdm2 is related to dynamic movements in these regions.
authors: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica Farmaceutica e Biologica, Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy. annamaria.almerico@unipa.it
authors: Anna Maria
authors: AM
authors: Almerico
authors: Marco
authors: M
authors: Tutone
authors: Licia
authors: L
authors: Pantano
authors: Antonino
authors: A
authors: Lauria
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry*; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D001569:Benzodiazepines; D051736:Proto-Oncogene Proteins c-mdm2