Williams Shawn P, Kuyper Lee F, Pearce Kenneth H
Department of Computational, Analytical and Structural Sciences, GlaxoSmithKline Discovery Research, Research Triangle Park, NC 27709, USA.
Curr Opin Chem Biol. 2005 Aug;9(4):371-80. doi: 10.1016/j.cbpa.2005.06.007.
Technological advances to increase the throughput of purified protein production and co-crystallization of target proteins with small molecules have helped to solidify the role that structure via crystallography has on drug discovery. Visualization of how drug-like molecules bind to the target protein is a key step in driving follow-up or preclinical chemistry to improve characteristics of the molecule. Using structural information to guide small-molecule design and generate new chemical ideas is now a mainstay in the drug discovery process.
提高纯化蛋白产量以及目标蛋白与小分子共结晶通量的技术进步,有助于巩固晶体学结构在药物发现中的作用。了解类药物分子如何与目标蛋白结合是推动后续或临床前化学研究以改善分子特性的关键一步。利用结构信息指导小分子设计并产生新的化学思路,现已成为药物发现过程的支柱。