Prostate cancer continues to pose a public health challenge to the United States. It's the most commonly diagnosed cancer and second leading cause of cancer related deaths in U.S. males with approximately 240,000 new cases and 34,000 deaths in 2011. Initially, prostate cancer begins as an androgen-dependent tumor. Over time, prostate cancer eventually progresses or emerges to an androgen independent or refractory state for which there is no effective treatment. Small molecules such as dibenzoylmethane (DBM) which specifically target the glucocorticoid receptor (GR) signaling pathway may provide an effective treatment for hormone refractory prostate cancer. Computational and modeling data suggest that DBM interacts within different locations on the GR. Molecular models were constructed based on the crystal structure of human GR-LBD in the complex of a glucocorticoid (GC) ligand using the Molecular Operating Environment (MOE). Models were obtained from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RSCB PDB). Alternate binding sites for DBM based on DBM conformation within the GR-LBD binding pocket will be explored using the docking tool in the MOE software. Protein alignment will be utilized to compare the conformation of GR-LBD in complex with DBM and the conformation of the protein when a GC is bound. Binding affinities and conformation energies will be calculated for each ligand-protein complex for overall good fit. The amino acid sequence of the DBM-GR binding site will be determined using the sequence editor tool in MOE. This will provide information on changes in protein conformation and ligand affinity that occur in the presence of DBM.

Computational modeling of dietary dibenzoylmethane for targeting GR binding sites in hormone refractory prostate cancer

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.