The novel anti-cancer feature of Brazzein through activating of hTLR5 by integration of biological evaluation: molecular docking and molecular dynamics simulation.

Many of plant proteins exhibit the properties similar to the antitumor proteins although the anticancer activity of Brazzein on modulating the autophagy signaling pathway has not been determined so far. The present study aimed to develop a simplified system to enable the rational design of the activating extracellular domain of human Toll-like receptor 5 (hTLR5). To identify the anticancer effect of Brazzein, HADDOCK program and molecular dynamics (MD) simulation were applied to examine the binding of the wild type (WT) and p.A19K mutant of Brazzein to the TLR5. The expression of MAP1S and TNF-α genes was estimated based on real-time PCR. The results clearly confirmed that the WT of Brazzein activated hTLR5 in the MCF-7 cell line since the genes were more and significantly less expressed in the cells treated with the WT and p.A19K mutant than the control, respectively. The snapshots of MD simulation exhibit the consistent close interactions of hTLR5 with the two helices of Brazzein on its lateral side. The results of per residue-free energy decomposition analysis substantiate those of intermolecular contact analysis perfectly one. We propose that the WT of Brazzein can act as an antitumor drug candidate.