Sørensen Jesper, Demir Özlem, Swift Robert V, Feher Victoria A, Amaro Rommie E
Department of Chemistry and Biochemistry, University of California, 3234 Urey Hall, MC-0340, San Diego, La Jolla, CA, 92093-0340, USA.
Methods Mol Biol. 2015;1215:445-69. doi: 10.1007/978-1-4939-1465-4_20.
It is widely accepted that protein receptors exist as an ensemble of conformations in solution. How best to incorporate receptor flexibility into virtual screening protocols used for drug discovery remains a significant challenge. Here, stepwise methodologies are described to generate and select relevant protein conformations for virtual screening in the context of the relaxed complex scheme (RCS), to design small molecule libraries for docking, and to perform statistical analyses on the virtual screening results. Methods include equidistant spacing, RMSD-based clustering, and QR factorization protocols for ensemble generation and ROC analysis for ensemble selection.
人们普遍认为，蛋白质受体在溶液中以多种构象的集合形式存在。如何将受体的灵活性最佳地纳入用于药物发现的虚拟筛选方案中，仍然是一个重大挑战。本文描述了逐步方法，用于在松弛复合物方案（RCS）的背景下生成和选择用于虚拟筛选的相关蛋白质构象，设计用于对接的小分子文库，并对虚拟筛选结果进行统计分析。方法包括用于集合生成的等距间距、基于均方根偏差（RMSD）的聚类和QR分解协议，以及用于集合选择的ROC分析。
