Fundamental reaction pathway and free energy profile for inhibition of proteasome by Epoxomicin.

@article{Wei2012FundamentalRP,
  title={Fundamental reaction pathway and free energy profile for inhibition of proteasome by Epoxomicin.},
  author={Donghui Wei and Beilei Lei and Mingsheng Tang and Chang-Guo Zhan},
  journal={Journal of the American Chemical Society},
  year={2012},
  volume={134 25},
  pages={10436-50}
}
First-principles quantum mechanical/molecular mechanical free energy calculations have been performed to provide the first detailed computational study on the possible mechanisms for reaction of proteasome with a representative peptide inhibitor, Epoxomicin (EPX). The calculated results reveal that the most favorable reaction pathway consists of five steps. The first is a proton transfer process, activating Thr1-O(γ) directly by Thr1-N(z) to form a zwitterionic intermediate. The next step is… CONTINUE READING