Stout T J, Foster P G, Matthews D J
Exelixis Inc., 170 Harbor Way, S. San Francisco, CA 94080, USA.
Curr Pharm Des. 2004;10(10):1069-82. doi: 10.2174/1381612043452695.
Structural biology is an invaluable tool in modern drug discovery, providing key insights into the interactions of small-molecule drugs with their protein targets. As in many aspects of the drug discovery process, significant synergies can be realized in structural biology by the contemporaneous pursuit of many target proteins from a single structural and functional class. We will review some of those synergies here using the example of the protein kinases--an important class of drug targets that has recently been the subject of intensive study. We conclude by discussing some of the technical advances in X-ray crystallography that have enabled implementation of high-throughput structural biology as applied to drug lead optimization.
结构生物学是现代药物研发中一项极具价值的工具，它能为小分子药物与其蛋白质靶点之间的相互作用提供关键见解。正如在药物研发过程的许多方面一样，通过同时研究来自单一结构和功能类别的多种靶蛋白，结构生物学能够实现显著的协同效应。我们将以蛋白激酶为例，在此回顾其中的一些协同效应。蛋白激酶是一类重要的药物靶点，近期一直是深入研究的对象。最后，我们将讨论X射线晶体学的一些技术进展，这些进展使得高通量结构生物学得以应用于药物先导物优化。
