An Efficient and Versatile Tool for Automatic Fragment-Based Design
【摘要】：In structure-based drug design, automated de novo design methods are helpful tools for lead discovery as well as lead optimization. In a previous study(J. Chem. Inf.Model., 2011, 51, 1474–1491), we reported a new de novo design method, namely Automatic Tailoring and Transplanting(AutoTT). It overcomes some intrinsic problems in conventional fragment-based build-up methods. In this study, we describe an upgraded version, i.e. AutoTT2. Structural operations conducted by AutoTT2 have been largely optimized by introducing several new algorithms. As result, its overall efficiency in multi-round optimization jobs has been speeded up by a few thousand folds. With this improvement, it is now practical to conduct structural crossover among multiple lead molecules by using AutoTT2. Three different test cases are described in this study, which demonstrate the new features and versatile applications of AutoTT2. The AutoTT2 software suite is available to the public.Besides, a web portal for running AutoTT2 on-line is provided at http://www.sioc-ccbg.ac.cn/software/att2 for testing.