Adding calorimetric data to decision making in lead discovery: a hot tip
Adding calorimetric data to decision making in lead discovery: a hot tip
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DOI：
10.1038/nrd3054
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发表时间：
2010-01-01
影响因子：
120.1
通讯作者：
Freire, Ernesto
中科院分区：
文献类型：
--
作者：
Ladbury, John E.;Klebe, Gerhard;Freire, Ernesto
认识到高通量筛选方法在发现候选药物方面的局限性，重新唤起了人们对基于结构和其他合理设计方法的兴趣。在这里，我们描述了如何等温滴定量热法可以用来获得热力学数据的化合物结合蛋白质的目标。我们建议，这些数据-特别是焓的变化-可以提供一个有价值的，补充除了既定的工具，用于选择化合物的铅发现和帮助铅优化。
Recognition of the limitations of high-throughput screening approaches in the discovery of candidate drugs has reawakened interest in structure-based and other rational design methods. Here, we describe how isothermal titration calorimetry can be used to obtain thermodynamic data on the binding of compounds to protein targets. We propose that these data - particularly the change in enthalpy - could provide a valuable, complementary addition to established tools for selecting compounds in lead discovery and for aiding lead optimization.