Challenges and opportunities for new protein crystallization strategies in structure-based drug design.
Challenges and opportunities for new protein crystallization strategies in structure-based drug design.
复制标题
DOI：
10.1517/17460441.2010.515583
复制
发表时间：
2010-11
影响因子：
6.3
通讯作者：
Thompson DH
中科院分区：
文献类型：
--
作者：
Grey JL;Thompson DH
基于结构的药物设计（SBDD）已经成为一种有价值的药物先导发现工具，显示出加速发现过程的潜力，同时降低开发成本并提高最终选择的药物的效力。SBDD是一个迭代的、理性的先导化合物雕刻过程，既包括新衍生物的合成，也包括通过计算对接或阐明目标结构与先导化合物的配合物来评估它们与目标结构的结合。该方法在很大程度上依赖于在存在或不存在候选药物的情况下，通过x射线晶体学分析获得药物靶标的高分辨率（< 2Å）三维结构。缺乏生产高质量晶体的通用方法仍然是大分子结晶过程中的主要瓶颈。本文简要介绍了SBDD技术，并介绍了几种大分子结晶策略，重点介绍了目前该领域的研究进展和面临的挑战。本文还讨论了更普遍的大分子结晶技术的最新发展趋势，特别是适用于可溶性和整体膜蛋白的基于核的技术。
Structure-based drug design (SBDD) has emerged as a valuable pharmaceutical lead discovery tool, showing potential for accelerating the discovery process, while reducing developmental costs and boosting potencies of the drug that is ultimately selected. SBDD is a iterative, rational, lead compound sculpting process that involves both the synthesis of new derivatives and the evaluation of their binding to the target structure either through computational docking or elucidation of the target structure as a complex with the lead compound. This method heavily relies on the production of high-resolution (< 2Å) three-dimensional structures of the drug target, obtained through X-ray crystallographic analysis, in the presence or absence of the drug candidate. The lack of generalized methods for high quality crystal production is still a major bottleneck in the process of macromolecular crystallization. This review provides a brief introduction to SBDD and describes several macromolecular crystallization strategies, with an emphasis on advances and challenges facing researchers in the field today. Recent trends in the development of more universal macromolecular crystallization techniques, particularly nucleation-based techniques that are applicable to both soluble and integral membrane proteins, are also discussed.
登录
查看更多内容
影响因子：
7.3
作者：
Ghosh AK;Takayama J;Aubin Y;Ratia K;Chaudhuri R;Baez Y;Sleeman K;Coughlin M;Nichols DB;Mulhearn DC;Prabhakar BS;Baker SC;Johnson ME;Mesecar AD
通讯作者：
Mesecar AD
影响因子：
--
作者：
Ghosh, Arun K.;Xi, Kai;Johnson, Michael E.;Baker, Susan C.;Mesecar, Andrew D.
通讯作者：
Mesecar, Andrew D.
新的配体和靶标的对接和化学信息筛选。
影响因子：
7.7
作者：
Kolb, Peter;Ferreira, Rafaela S.;Irwin, John J.;Shoichet, Brian K.
通讯作者：
Shoichet, Brian K.
影响因子：
56.9
作者：
Liu, XG;Zhang, Y;Mirkin, CA
通讯作者：
Mirkin, CA
影响因子：
15
作者：
Kreutz JE;Li L;Roach LS;Hatakeyama T;Ismagilov RF
通讯作者：
Ismagilov RF