Tsai Yingssu, McPhillips Scott E, González Ana, McPhillips Timothy M, Zinn Daniel, Cohen Aina E, Feese Michael D, Bushnell David, Tiefenbrunn Theresa, Stout C David, Ludaescher Bertram, Hedman Britt, Hodgson Keith O, Soltis S Michael
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Stanford University, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):796-803. doi: 10.1107/S0907444913001984. Epub 2013 Apr 11.
AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully demonstrated. This workflow was run once on the same 96 samples that the group had examined manually and the workflow cycled successfully through all of the samples, collected data from the same samples that were selected manually and located the same peaks of unmodeled density in the resulting difference Fourier maps.
AutoDrug是一款基于科学工作流程范式的软件，它集成了斯坦福同步辐射光源大分子晶体学光束线和第三方处理软件，以自动化基于片段的药物发现过程中的晶体学步骤。AutoDrug会筛选一组浸泡有片段的晶体，根据筛选结果和用户指定的标准选择用于数据收集的晶体，并确定最佳的数据收集策略。然后，它收集并处理衍射数据，使用提供的模型进行分子置换，并检测可能由结合片段产生的电子密度。所有过程都是完全自动化的，即在没有用户交互或监督的情况下执行。样品可以按照特定的蛋白质、晶体形式和/或浸泡条件进行分组筛选。一次AutoDrug运行仅受光束线样品储存杜瓦瓶容量的限制：目前为288个样品。AutoDrug是与一个新的科学工作流程自动化框架RestFlow一起开发的。RestFlow通过管理数据流和结果组织以及编排计算管道步骤的执行，简化了AutoDrug的设计。它还简化了第三方程序与光束线控制系统的执行和交互。将AutoDrug建模为科学工作流程能够开发和支持满足不同用户群体需求的多种变体。一个专门模仿CoCrystal Discovery Inc.药物发现管道中晶体学阶段的工作流程已经部署并成功展示。该工作流程在该团队手动检查过的相同96个样品上运行了一次，并且该工作流程成功地循环处理了所有样品，从手动选择的相同样品中收集了数据，并在所得的差值傅里叶图中定位了相同的未建模密度峰。
