Chppter 30. Recent advances in virtual ligand screening

This chapter discusses recent advances made in virtual ligand screening. Random high-throughput screening as a means for finding novel lead compounds against a variety of potential therapeutic targets is a widely accepted technique in modern drug discovery. Virtual ligand screening based on high-throughput protein-ligand docking and three-dimensional pharmacophore queries for the identification of compounds from databases provides a computational approach for the identification of novel compounds. These two techniques are often complementary. Pharmacophore searching methods are most often employed when the 3D structure of a target enzyme or receptor is not available, but a small number of active compounds are known. On the other hand, database docking methods are routinely used when an X-ray structure of the target protein is available. The chapter focuses on recent advances made in the use of two main 3D virtual ligand screening techniques: pharmacophore derived and protein-ligand docking methods, with an emphasis on results, rather than methodology development. It also discusses selected cases where a pharmacophore model or receptor structural information has been used in a search for novel lead matter and the virtual hits have been verified by one or more biological tests.