Discovery & Synthesis Chemputer: An intelligent universal system for automated chemical synthesis and discovery across different hardware and scales

项目摘要 在这个合作项目中，我们将开发一个用于自动化和执行化学反应的系统 在一系列硬件和规模的已知和未知分子的合成。这项工作将 利用我们实验室在Chemputer（可编程化学合成）上过去6年的进展 机器人）和化学合成原理（化学合成的概念，表示在一种类型的化学 代码可以在任何兼容的硬件上可靠地运行）。提出了三个具体目标：1。发展 将运行合成方案的化学编程语言标准; 2.模块化插头的研制 以及用于化学合成的游戏硬件，包括与第三方系统的接口; 3.产生反应 化学合成和发现的筛选系统。这些目标将在五年期内制定 与NCATS进行高度整合和协作。在第1-2年，我们将致力于 所有三个具体目标，通过开发规范，实施计划，原型，测试集成概念， 接下来的3-5年，将在NCATS进行部署、集成和测试。发展中 一种用于化学合成的操作程序设计语言，它可以指定反应的要求 准确地说，我们将确保可编程化学，如计算，可以成为通用的兼容 硬件.我们将开发的编程语言是基于我们的化学描述语言，χDL（1.0）， which哪一个is open开源source源.我们将引入更强大的功能，例如，for循环和if when条件， χDL（2.0）将等同于一种函数式计算机编程语言，但不是用于 计算，χDL（2.0）将用于化学操作。这一功能升级非常重要，因为 语言将变得更加便携和通用。这是因为语言将不依赖于 外部语言不适合化学自动化。该系统将在格拉斯哥和NCATS进行确认 使用一系列涵盖有机化学范围的众所周知的反应，并将涉及几种情况 这些研究展示了新发现的化学物质是如何被编码的。我们还将探讨一系列 合成规模和使用现有技术的液-液和固-液萃取系统的新方法 用于纯化和文库开发的膜技术。该系统将用于优化现有的 化学反应和目标，以及使用机器学习系统探索新的目标。模块化 分析软件系统桥将包括NMR、IR、MS和HPLC，以提供实时反馈。项目 成果将是新化学实体的识别、设计、合成和验证作为起点 用于新靶点的药物开发，以及用于药物筛选的化学空间的扩展。的 该项目将在NCATS和格拉斯哥有一个领导，团队将与管理层联合协调 每个月都将举行正式会议的团队，经常每周和每两周举行一次会议，每季度举行一次会议 评论.一个指导委员会将审查进展情况，并向各小组提供咨询意见。

Project Summary In this collaborative project we will develop a system for the automation and execution of chemical reactions across a range of hardware and scales for the synthesis of known and unknown molecules. This work will leverage the last 6 years of progress in our laboratory on the Chemputer (a programmable chemical synthesis robot) and the principle of Chemputation (the concept that a chemical synthesis expressed in a type of chemical code can be run on any compatible hardware reliably). Three specific aims are proposed: 1. To develop the chemical programming language standard that will run the synthesis protocols; 2. Development of modular plug and play hardware for chemical synthesis including interfaces to 3rd party systems; 3. Creation of a reaction screening system for chemical synthesis and discovery. These aims will be developed over the five-year period in a highly integrated and collaborative working modus operandi with NCATS. During years 1-2 we will work on all three Specific Aims by developing specifications, implementation plans, prototypes, test integration concepts, and this will be followed by, in years 3-5, cycles of deployment, integration, and testing at NCATS. By developing an operational programming language for chemical synthesis that can specify the requirements for the reactions precisely, we will ensure that programmable chemistry, like computation, can become universal on compatible hardware. The programming language we will develop is based on our chemical description language, χDL (1.0), which is open source. We will introduce more powerful functions e.g., for loops and if when conditions so that χDL (2.0) will be equivalent to a functional computer programming language, but rather than being used for computation, χDL (2.0) will be for chemical operations. This upgrade in functionality is important since the language will become more portable and universal. This is because the language will not be dependent upon external languages not suitable for chemistry automation. This system will be validated at Glasgow and NCATS using a range of well-known reactions covering the span of organic chemistry and will involve several case studies demonstrating how newly discovered chemistry can be encoded. We will also explore a range of synthesis scales and new approaches to liquid-liquid and solid-liquid extraction systems using state of the art membrane technologies for purification and library development. The system will be used to optimise existing chemical reactions and targets as well as explore for new targets using a machine learning system. A modular analytics software system-bridge will include NMR, IR, MS, and HPLC to provide real-time feedback. The project outcomes will be the identification, design, synthesis, and validation of new chemical entities as starting points for drug development of novel targets, and the expansion of chemical space available for drug screening. The project will have a lead at NCATS and Glasgow, and the teams will be jointly coordinated with a management team that will be meeting formally every month, with frequent weekly and bi-weekly meetings, and quarterly reviews. A steering committee will review progress and give advice to the teams.