Computer aided drug studies of BH3 derivatives as anti-cancer agents against Bcl-xL receptor

摘要

Informatics and computational design methods were used to create new molecules that could potentially bind antiapoptotic proteins, thus promoting death of cancer cells. Apoptosis is a cellular process that leads to the death of damaged cells. Its malfunction can cause cancer and poor response to conventional chemotherapy. After being activated by cellular stress signals, proapoptotic proteins bind antiapoptotic proteins, thus allowing apoptosis to go forward. Molecular docking is routinely used for understanding the drug-receptor interactions in modern drug design. Here we described the docking of BH3 derived peptides from BID as inhibitors to Bcl-xL, which is over expressed in cancerous cells. The inhibitory activities against Bcl-xL were investigated by molecular docking using Hex docking software. All the designed peptides were showed good binding energy, among which GDGVQ & VGDGV are showed moderate binding energy (-277.94 & -258.24 respectively) and satisfied reasonably the Lipinski Rule of Five and ADME/T properties. Further modifications are needed for these designed compounds to increase its docking score as well as properties and finally we planned to synthesis and also screen for invitro anti cancerous effect.