@article{ZuoGandhiArndtetal.2012,
  author    = {Zuo, Zhili and Gandhi, Neha S. and Arndt, Katja Maren and Mancera, Ricardo L.},
  title     = {Free energy calculations of the interactions of c-Jun-based synthetic peptides with the c-Fos protein},
  series = {Biopolymers},
  volume    = {97},
  journal   = {Biopolymers},
  number    = {11},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0006-3525},
  doi       = {10.1002/bip.22099},
  pages     = {899 -- 909},
  year      = {2012},
  abstract  = {The c-Fosc-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.},
  language  = {en}
}