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.
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.
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|Item Type:||Journal Article|
|Keywords:||free energy of binding; coiled-coil; molecular dynamics; MM/GBSA; leucine zipper|
|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|
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