title: The genesis of high-throughput structure-based drug discovery using protein crystallography.
abstract: Over the past 12 years, drugs have been developed using structure-based drug design relying upon traditional crystallographic methods. Established successes, such as the drugs designed against HIV-1 protease and neuraminidase, demonstrate the utility of a structure-based approach in the drug-discovery process. However, the approach has historically lacked throughput and reliability capabilities; these bottlenecks are being overcome by breakthroughs in high-throughput structural biology. Recent technological innovations such as submicroliter high-throughput crystallization, high-performance synchrotron beamlines and rapid binding-site analysis of de novo targets using virtual ligand screening and small molecule co-crystallization have resulted in a significant advance in structure-based drug discovery.
authors.affiliation: Stanford Synchrotron Radiation Laboratory, Stanford University, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kuhn
authors.forename: Keith
authors.initials: K
authors.lastname: Wilson
authors.forename: Marianne G
authors.initials: MG
authors.lastname: Patch
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Stevens
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011506:Proteins