Crystallization to obtain protein-ligand complexes for structure-aided drug design
Crystallization to obtain protein-ligand complexes for structure-aided drug design
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DOI：
10.1107/s0907444906012601
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发表时间：
2006-06-01
期刊：
影响因子：
--
通讯作者：
Danley, Dennis E.
中科院分区：
文献类型：
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作者：
Danley, Dennis E.
使用X射线晶体学来获得用于结构辅助药物设计（SADD）的三维结构是当今药物发现中的常见活动。在这个过程中，与其大分子靶标复合的抑制剂或其他感兴趣的配体的结构被求解，并且结构信息被迭代地用于设计新的分子。在靶蛋白和配体之间形成共晶复合物的能力对于该过程是必不可少的，因此对于在该领域中实践的任何人都是相当感兴趣的。在获得必要的配体-蛋白质晶体的过程中，即使对于目的蛋白质充分建立了结晶条件，通过共结晶或浸泡获得具有抑制剂的共结构也常常不成功。有许多潜在的原因，这种缺乏成功，本文概述了一些可能涉及的因素，并讨论了设计成功的实验，以获得迭代costructures时应考虑的因素。
The use of X-ray crystallography to derive three-dimensional structures for structure-aided drug design ( SADD) is a common activity in drug discovery today. In this process, the structures of inhibitors or other ligands of interest complexed with their macromolecular target are solved and the structural information is used iteratively to design new molecules. The ability to form cocrystal complexes between a target protein and a ligand is essential to this process and therefore is of considerable interest to anyone practicing in this field. In the course of obtaining the necessary ligand-protein crystals, even with crystallization conditions well established for a protein of interest, obtaining co-structures with inhibitors either through cocrystallization or soaking is too often not successful. There are numerous potential reasons for this lack of success and this article outlines a number of possible factors that may be involved and discusses considerations that should be taken into account when designing successful experiments to obtain iterative costructures.