It has been indicated that
tumor necrosis factor receptor-associated factor-6 (
TRAF6) will upregulate the expression of
hypoxia-inducible factor-1α (HIF-1α) and promote
tumor angiogenesis.
TRAF6 proteins can be treated as
drug target
proteins for a differentiation
therapy against
cancers. As structural disordered disposition in the
protein may induce the side-effect and reduce the occupancy for
ligand to bind with target
protein, PONDR-Fit protocol was performed to predict the disordered disposition in
TRAF6 protein before virtual screening. TCM compounds from the TCM Database@Taiwan were employed for virtual screening to identify potent compounds as lead compounds of
TRAF6 inhibitor. After virtual screening, the MD simulation was performed to validate the stability of interactions between
TRAF6 proteins and each
ligand. The top TCM compounds,
tryptophan,
diiodotyrosine, and
saussureamine C, extracted from Saussurea lappa Clarke, Bos taurus domesticus Gmelin, and Lycium chinense Mill., have higher binding affinities with target
protein in docking simulation. However, the docking pose of
TRAF6 protein with
tryptophan is not stable under dynamic condition. For the other two TCM candidates,
diiodotyrosine and
saussureamine C maintain the similar docking poses under dynamic conditions. Hence, we propose the TCM compounds,
diiodotyrosine and
saussureamine C, as potential candidates as lead compounds for further study in
drug development process with the
TRAF6 protein against
cancer.