Computer Simulations Reveal the Structure and Dynamics of a Chemical Signal that Triggers Metastatic Cancer

San Diego Supercomputer Center (SDSC) McCammon Lab UC San Diego University of Pavia, Italy National Institutes of Health Howard Hughes Medical Institute National Science Foundation UCSD-University of Pavia team say insights into the "packaging" of DNA could lead to new "epigenetic" drugs that block the spread of cancer cells February 08, 2011 By Warren Froelich Molecular Dynamics simulation shows that oxygen molecules reach the active site of Lysine Specific Demethylase 1 although substrate peptides (black, H3 histone tail & orange, SNAIL1 protein) are bound (Riccardo Baron et al. UC San Diego) In cancer and other pathological diseases, researchers are discovering that packaging is important: specifically, how DNA - about two meters long when unwound and stretched - coils up and compacts neatly inside the nucleus of a cell. What they've learned is that molecular signals that control the packaging of DNA are critical to the activation and silencing of genes in the human body - a process generally described as epigenetics. Now, a team of researchers from UC San Diego and the University of Pavia in Italy, with the help of high-performance computers housed at the San Diego Supercomputer Center (SDSC), have captured the chemical structure of one such signal - in static crystal form and in motion - which is at the heart of a variety of morphological events including the rapid movement of cells during embryonic development, wound healing, and cancer. The results offer a potentially new path to combat metastatic cancer by blocking the activity of this epigenetic signal, which, among other things, has been shown to silence a gene responsible for cell-to-cell adhesion, a "molecular glue," thus allowing cancer cells to spread.