RANK ligand (RANKL) is a key mediator of osteoclast formation, function, and survival. Therefore, RANKL is thought to be responsible for osteoclast-mediated bone resorption in a broad range of disorders such as postmenopausal osteoporosis and cancer-induced bone disease. Moreover, RANKL has been implicated as a primary mediator of bone erosions, a hallmark of rheumatoid arthritis (RA). Denosuma...

Osteoprotegerin (OPG) binds the ligand for receptor activator of nuclear factor kappa B (RANKL) to prevent association with its receptor RANK and inhibit osteoclast-mediated bone resorption. OPG has been reported, recently, to inhibit TNF-related apoptosisinduced ligand (TRAIL)-induced tumor cell apoptosis. This raises the possibility that OPG may play a unique role in regulating these two sign...

Hypercalcemia is one of the most frequent and serious complications in patients with adult T-cell leukemia (ATL) and is due to marked bone resorption by accumulation of osteoclasts (OCLs). Although several cytokines such as interleukin 1 and parathyroid hormone-related protein are thought to be involved in the development of high serum Ca(++) levels, its precise underlying mechanism remains unk...

Predicting relative protein-ligand binding affinities is a central pillar of lead optimization efforts in structure-based drug design. The Site Identification by Ligand Competitive Saturation (SILCS) methodology based on functional group affinity patterns the form free energy maps that may be used to compute poses and affinities. In present study, we analyze, compare discuss results obtained fr...

BACKGROUND In drug design, an efficient structure-based optimization of a ligand needs the precise knowledge of the protein-ligand interactions. In the absence of experimental information, docking programs are necessary for ligand positioning, and the choice of a reliable program is essential for the success of such an optimization. The performances of four popular docking programs, Gold, Glide...