TY  - JOUR
A1  - Zuo, Zhili
A1  - Gandhi, Neha S.
A1  - Arndt, Katja Maren
A1  - Mancera, Ricardo L.
T1  - Free energy calculations of the interactions of c-Jun-based synthetic peptides with the c-Fos protein
T2  - Biopolymers
N2  - 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.
KW  - free energy of binding
KW  - coiled-coil
KW  - molecular dynamics
KW  - MM
KW  - GBSA
KW  - leucine zipper
Y1  - 2012
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/35570
SN  - 0006-3525
VL  - 97
IS  - 11
SP  - 899
EP  - 909
PB  - Wiley-Blackwell
CY  - Hoboken
ER  -