Advances in structure-based drug design

摘要

Over the past two decades, technological advancements in experimental methods such as NMR and X-ray crystallography have allowed structure-based drug design (SBDD) to obtain a vital position in medicinal chemistry. Owing to the dramatic increase in the availability of 3D structure of protein targets and the rapid advancement in computational chemistry, SBDD has become an integral strategy for both lead generation and lead optimization. In addition, computer-aided molecular docking has some significant advantages over traditional high-throughput screening (HTS). Medicinal chemists now have access to structural information on small molecule candidates bound to the therapeutic target within days of compound synthesis. SBDD permits the creation of new ligands with stepwise assembly of atoms or molecular fragments that conform to the binding pocket. This ability to generate novel structures not found in any database has cemented SBDD a crucial method for modern drug discovery.