结构基因组学与药物发现。
Structural genomics and drug discovery.
作者信息
Lundstrom K
机构信息
Flamel Technologies, 33 Avenue du Dr. Georges Lévy, 69693 Vénissieux, France.
出版信息
J Cell Mol Med. 2007 Mar-Apr;11(2):224-38. doi: 10.1111/j.1582-4934.2007.00028.x.
Abstract
Structure determination has already proven useful for lead optimization and direct drug design. The number of high-resolution structures available in public databases today exceeds 30,000 and will definitely aid in structure-based drug design. Structural genomics approaches covering whole genomes, topologically similar proteins or gene families are great assets for further progress in the development of new drugs. However, membrane proteins representing 70% of current drug targets are poorly characterized structurally. The problems have been related to difficulties in obtaining large amount of recombinant membrane proteins as well as their purification and structure determination. Structural genomics has proven successful in developing new methods in areas from expression to structure determination by studying a large number of target proteins in parallel.
摘要
结构测定已被证明对先导化合物优化和直接药物设计有用。如今公共数据库中可用的高分辨率结构数量超过30000个，这肯定有助于基于结构的药物设计。涵盖全基因组、拓扑相似蛋白质或基因家族的结构基因组学方法是新药开发取得进一步进展的宝贵资源。然而，占当前药物靶点70%的膜蛋白在结构上的特征却很不完善。这些问题与获取大量重组膜蛋白及其纯化和结构测定方面的困难有关。通过并行研究大量目标蛋白，结构基因组学已在从表达到结构测定等领域成功开发出了新方法。
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