Utility of homology models in the drug discovery process.
Utility of homology models in the drug discovery process.
复制标题
DOI：
10.1016/s1359-6446(04)03196-4
复制
发表时间：
2004-08-01
影响因子：
7.4
通讯作者：
Hilgenfeld R
中科院分区：
文献类型：
--
作者：
Hillisch A;Pineda LF;Hilgenfeld R
现代同源建模技术应用于药物靶蛋白结构的全基因组预测，为提高制药行业药物发现过程的有效性提供了真正的机会。生物信息学和蛋白质建模算法的进步，以及实验蛋白质结构信息的巨大增加，有助于生成包含已知基因组蛋白质序列的重要部分的同源模型的数据库。目前，可以为所有已知蛋白质生成高达56%的三维结构信息。然而，关于同源模型在药物设计中的真正价值存在相当大的争议。本文综述了这一领域的最新发展，包括同源建模技术在药学相关问题上的成功应用实例。此外，还讨论了在药物发现过程的各个阶段应用同源模型的优势和局限性。
Modern homology modeling techniques applied for the genome-wide prediction of drug target protein structures represent a real chance for an enhancement in the effectiveness of the drug discovery process in the pharmaceutical industry. Advances in bioinformatics and protein modeling algorithms, in addition to the enormous increase in experimental protein structure information, have aided in the generation of databases that comprise homology models of a significant portion of known genomic protein sequences. Currently, 3D structure information can be generated for up to 56% of all known proteins. However, there is considerable controversy concerning the real value of homology models for drug design. This review provides an overview of the latest developments in this area and includes selected examples of successful applications of the homology modeling technique to pharmaceutically relevant questions. In addition, the strengths and limitations of the application of homology models during all phases of the drug discovery process are discussed.