Kuhn Peter, Wilson Keith, Patch Marianne G, Stevens Raymond C
Stanford Synchrotron Radiation Laboratory, Stanford University, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
Curr Opin Chem Biol. 2002 Oct;6(5):704-10. doi: 10.1016/s1367-5931(02)00361-7.
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.
在过去的12年里，人们利用基于结构的药物设计并依靠传统晶体学方法开发药物。已取得的成功，如针对HIV-1蛋白酶和神经氨酸酶设计的药物，证明了基于结构的方法在药物发现过程中的实用性。然而，从历史上看，这种方法缺乏通量和可靠性；高通量结构生物学的突破正在克服这些瓶颈。最近的技术创新，如亚微升高通量结晶、高性能同步加速器光束线以及使用虚拟配体筛选和小分子共结晶对全新靶点进行快速结合位点分析，已使基于结构的药物发现取得了重大进展。
