Issue 7, 2011

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

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

Article information

Article type
Paper
Submitted
11 ágú. 2010
Accepted
27 okt. 2010
First published
10 des. 2010

Phys. Chem. Chem. Phys., 2011,13, 2738-2743

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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements