Free Energy Calculations of the Interactions of c-Jun-based Synthetic Peptides with the c-Fos Protein
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Free energy of binding of coiled-coil complexes with different electrostatic environments: the influence of force field polarisation and cappingZhuo, Z.; Guo, L.; Mancera, Ricardo (2014)Coiled-coils are well known protein–protein interaction motifs, with the leucine zipper region of activator protein-1 (AP-1) consisting of the c-Jun and c-Fos proteins being a typical example. Molecular dynamics (MD) ...
Lazoura, E.; Lodding, J.; Farrugia, W.; Day, S.; Ramsland, Paul; Apostolopoulos, V. (2009)The major histocompatibility complex (MHC) on the surface of antigen presenting cells functions to display peptides to the T cell receptor (TCR). Recognition of peptide-MHC by T cells initiates a cascade of signals, which ...
Cendron, A.; Wines, B.; Brownlee, R.; Ramsland, Paul; Pietersz, G.; Hogarth, P. (2008)A disulphide-constrained peptide that binds to the low affinity Fc receptor, Fc?RIIa (CD32) has been identified and its structure solved by NMR. Linear (7-mer and 12-mer) and disulphide-constrained (7-mer) phage display ...