Carvalho Ana Luísa, Trincão José, Romão Maria João
REQUIMTE, Department of Chemistry, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal.
Methods Mol Biol. 2009;572:31-56. doi: 10.1007/978-1-60761-244-5_3.
Macromolecular X-ray crystallography is an important and powerful technique in drug discovery, used by pharmaceutical companies in the discovery process of new medicines. The detailed analysis of crystal structures of protein-ligand complexes allows the study of the specific interactions of a particular drug with its protein target at the atomic level. It is used to design and improve drugs. The starting point of these studies is the preparation of suitable crystals of complexes with potential ligands, which can be achieved by using different strategies described in this chapter. In addition, an introduction to X-ray crystallography is given, highlighting the fundamental steps necessary to determine the three-dimensional structure of protein-ligand complexes, as well as some of the tools and criteria to validate crystal structures available in databases.
大分子X射线晶体学是药物研发中一项重要且强大的技术，制药公司在新药研发过程中会用到该技术。对蛋白质-配体复合物晶体结构的详细分析能够在原子水平上研究特定药物与其蛋白质靶点之间的具体相互作用。它用于设计和改进药物。这些研究的起点是制备含有潜在配体的复合物的合适晶体，这可以通过本章所述的不同策略来实现。此外，还介绍了X射线晶体学，重点阐述了确定蛋白质-配体复合物三维结构所需的基本步骤，以及数据库中用于验证晶体结构的一些工具和标准。
