Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein
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 affin...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Published: |
John Wiley and Sons, Inc.
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/43767 |
| _version_ | 1848756801526300672 |
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| author | Zuo, Zhili Gandhi, Neha Arndt, K. Mancera, Ricardo |
| author_facet | Zuo, Zhili Gandhi, Neha Arndt, K. Mancera, Ricardo |
| author_sort | Zuo, Zhili |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T09:17:58Z |
| format | Journal Article |
| id | curtin-20.500.11937-43767 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:17:58Z |
| publishDate | 2012 |
| publisher | John Wiley and Sons, Inc. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-437672017-09-13T13:41:45Z Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein Zuo, Zhili Gandhi, Neha Arndt, K. Mancera, Ricardo 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/43767 10.1002/bip.22099 John Wiley and Sons, Inc. restricted |
| spellingShingle | Zuo, Zhili Gandhi, Neha Arndt, K. Mancera, Ricardo Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein |
| title | Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein |
| title_full | Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein |
| title_fullStr | Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein |
| title_full_unstemmed | Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein |
| title_short | Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein |
| title_sort | free energy calculations of the interactions of c-jun-based synthetic peptides with the c-fos protein |
| url | http://hdl.handle.net/20.500.11937/43767 |