Free energy calculations of the interactions of c-Jun-based synthetic peptides with the c-Fos protein

Zuo, Zhili, Gandhi, Neha S., Arndt, Katja, & Mancera, Ricardo L. (2012) Free energy calculations of the interactions of c-Jun-based synthetic peptides with the c-Fos protein. Biopolymers, 97(11), pp. 899-909.

View at publisher


The c-Fos–c-Jun complex forms the activator protein 1 transcription factor, a therapeutic target in the treatment of cancer. Various synthetic peptides have been designed to try to selectively disrupt the interaction between c-Fos and c-Jun at its leucine zipper domain. To evaluate the binding affinity between these synthetic peptides and c-Fos, polarizable and nonpolarizable molecular dynamics (MD) simulations were conducted, and the resulting conformations were analyzed using the molecular mechanics generalized Born surface area (MM/GBSA) method to compute free energies of binding. In contrast to empirical and semiempirical approaches, the estimation of free energies of binding using a combination of MD simulations and the MM/GBSA approach takes into account dynamical properties such as conformational changes, as well as solvation effects and hydrophobic and hydrophilic interactions. The predicted binding affinities of the series of c-Jun-based peptides targeting the c-Fos peptide show good correlation with experimental melting temperatures. This provides the basis for the rational design of peptides based on internal, van der Waals, and electrostatic interactions.

Impact and interest:

4 citations in Scopus
Search Google Scholar™
4 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 93844
Item Type: Journal Article
Refereed: Yes
Keywords: free energy of binding; coiled-coil; molecular dynamics; MM/GBSA; leucine zipper
DOI: 10.1002/bip.22099
ISSN: 1097-0282
Divisions: Current > Schools > School of Mathematical Sciences
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2012 Wiley Periodicals, Inc.
Deposited On: 30 Mar 2016 23:12
Last Modified: 01 Apr 2016 00:09

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page