A model for the interaction of paclitaxel with the Bcl-2 loop domain: a chemical approach to induce conformation-dependent phosphorylation

A homology model for human Bcl-2 was built. Paclitaxel and baccatin III wer e individually docked into the Bcl-2 loop domain. The conformational space of the loop region on ligand binding was explored by molecular dynamics. Th e ligand-Bcl-2 interaction energy was calculated by minimization in the bin ding site. It was found that both paclitaxel's core skeleton and its C-13 s ide chain contribute significantly to its interaction with Bcl-2. A portion of the Bcl-2 loop domain was found to be locked by the bound paclitaxel an d baccatin III in a similar conformation.