Accelerated Communication

Abstract

Crystal structures of acetylcholinesterase complexed with ligands are compared with side-chain conformations accessed by native acetylcholinesterase in molecular dynamics (MD) simulations. Several crystallographic conformations of a key residue in a specific binding site are accessed in a simulation of native acetylcholinesterase, although not seen in rotomer plots. Conformational changes upon ligand binding thus involve preexisting equilibrium dynamics. Consequently, rational drug design could benefit significantly from conformations monitored by MD simulations of native targets.

Differential Modulation of Human Melanoma Cell Metalloproteinase Expression by α2β1 Integrin and CD44 Triple-helical Ligands Derived from Type IV Collagen

“…Approaches that interfere with CD44 binding to its ligand, such as administration of high molecular weight hyaluronic acid (HA), anti-CD44 mAb, or a CD44-receptor globulin, reduce tumor formation in the lung for animal models established from CD44-expressing tumor cell lines (36). Finally, proteolytic removal of CD44 inhibits the growth of primary tumors and curtails metastasis in a mouse B16 melanoma model (37).…”