Jump to main content
Jump to site search

Issue 7, 2011
Previous Article Next Article

Free energy evaluation of the p53-Mdm2 complex from unbinding work measured by dynamic force spectroscopy

Author affiliations

Abstract

The complex between the tumor suppressor p53 and its down-regulator Mdm2 has been studied by dynamic force spectroscopy and the unbinding data have been analyzed in the framework of the Jarzynski theoretical approach. Accordingly, the unbinding equilibrium free energy has been determined from the work done along several non-equilibrium paths from the bound to the unbound state in the single molecule regime. An unbinding free energy of −8.4 kcal mol−1 has been found for the complex; such a value is in a good agreement with that measured both in the bulk by isothermal titration calorimetry and that obtained from theoretical computing at the single molecule level. The determination of the unbinding free energy, together with the knowledge of the dissociation rate constant and energy barrier width, as previously obtained by dynamic force spectroscopy, adds rewarding insights on the energy landscape for this complex which is currently at the focus of anticancer drug design.

Graphical abstract: Free energy evaluation of the p53-Mdm2 complex from unbinding work measured by dynamic force spectroscopy

Back to tab navigation

Publication details

The article was received on 11 Aug 2010, accepted on 27 Oct 2010 and first published on 10 Dec 2010


Article type: Paper
DOI: 10.1039/C0CP01474E
Citation: Phys. Chem. Chem. Phys., 2011,13, 2738-2743
  •   Request permissions

    Free energy evaluation of the p53-Mdm2 complex from unbinding work measured by dynamic force spectroscopy

    A. R. Bizzarri and S. Cannistraro, Phys. Chem. Chem. Phys., 2011, 13, 2738
    DOI: 10.1039/C0CP01474E

Search articles by author

Spotlight

Advertisements