Li Yan, Zhao Zhixiong, Liu Zhihai, Su Minyi, Wang Renxiao
State Key Laboratory of Bioorganic and Natural Products Chemistry, Collaborative Innovation Center of Chemistry for Life Sciences, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai 200032, People's Republic of China.
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology , Macau, People's Republic of China.
J Chem Inf Model. 2016 Feb 22;56(2):435-53. doi: 10.1021/acs.jcim.5b00691. Epub 2016 Feb 3.
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.
2011 , 51 , 1474 - 1491 ) we reported a new de novo design method, namely, Automatic Tailoring and Transplanting (AutoT&T). It overcomes some intrinsic problems in conventional fragment-based buildup methods. In this study, we describe an upgraded version, namely, AutoT&T2. Structural operations conducted by AutoT&T2 have been largely optimized by introducing several new algorithms. As a result, its overall speed in multiround optimization jobs has been improved by a few thousand fold. With this improvement, it is now practical to conduct structural crossover among multiple lead molecules using AutoT&T2. Three different test cases are described in this study that demonstrate the new features and versatile applications of AutoT&T2. The AutoT&T2 software suite is available to the public. Besides, a Web portal for running AutoT&T2 online is provided at http://www.sioc-ccbg.ac.cn/software/att2 for testing.
在基于结构的药物设计中，自动从头设计方法是先导化合物发现和优化的有用工具。在之前的一项研究（《化学信息与建模杂志》：2011年，51卷，1474 - 1491页）中，我们报道了一种新的从头设计方法，即自动剪裁与移植（AutoT&T）。它克服了传统基于片段构建方法中的一些固有问题。在本研究中，我们描述了一个升级版，即AutoT&T2。通过引入几种新算法，AutoT&T2进行的结构操作已得到很大优化。结果，其在多轮优化任务中的整体速度提高了数千倍。有了这一改进，现在使用AutoT&T2在多个先导分子之间进行结构交叉变得可行。本研究描述了三个不同的测试案例，展示了AutoT&T2的新特性和广泛应用。AutoT&T2软件套件可供公众使用。此外，还提供了一个在线运行AutoT&T2的网站门户：http://www.sioc-ccbg.ac.cn/software/att2 用于测试。
