Structure-based drug design: From nucleic acid to membrane protein targets

The in silico methods for drug discovery are becoming increasingly powerful and useful. That, in combination 13 with increasing computer processor power, in our case using a novel distributed computing grid, has enabled 14 us to greatly enhance our virtual screening efforts. Herein we review some of these efforts using both 15 receptor and ligand-based virtual screening, with the goal of finding new anticancer agents. In particular, 16 nucleic acids are a neglected set of targets, especially the different morphologies of duplex, triplex, and 17 quadruplex DNA, many of which have increasing biological relevance. We also review examples of molecular 18 modeling to understand receptors and using virtual screening against G-protein coupled receptor membrane 19 proteins.