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

发现

• 批准号: 10632021
• 负责人: Lee Cronin
• 金额: $ 67.31万
• 依托单位: UNIVERSITY OF GLASGOW
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10632021
• 关键词: Algorithms; Architecture; Area; Automation; Behavior; Biochemistry; Biological; Case Study; Chemicals; Chemistry; Code; Collaborations; Computer Assisted; Computer software; Data; Data Correlations; Dedications; Development; Disparate; Drug Screening; Electronics; Elements; Ensure; Environment; Equipment; Feedback; Generations; Goals; High Pressure Liquid Chromatography; Individual; Intelligence; Laboratories; Language; Lead; Libraries; Link; Liquid substance; Machine Learning; Membrane; Methods; Modeling; National Center for Advancing Translational Sciences; Organic Chemistry; Outcome; Pharmaceutical Preparations; Phase; Play; Procedures; Process; Programming Languages; Protocols documentation; Reaction; Research; Robot; Running; Schedule; Solid; Specific qualifier value; Spectrum Analysis; Standardization; System; Technology; Testing; Time; Update; Validation; Work; analog; chemical reaction; chemical synthesis; computer program; design; digital; drug candidate; drug development; drug discovery; experimental study; improved; innovation; interest; invention; meetings; new chemical entity; novel; novel strategies; open source; operation; portability; programs; prototype; screening; simulation; software systems; spectroscopic data

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.

项目摘要 在这个协作项目中，我们将开发一个用于自动化和执行化学反应的系统 在一系列的硬件和尺度上，用于合成已知和未知分子。这项工作将 利用我们实验室的最后6年进度（可编程化学合成） 机器人）和化学原理（化学合成以一种化学物质表达的概念 代码可以可靠地在任何兼容的硬件上运行）。提出了三个具体目标：1。开发 化学编程语言标准将运行合成方案； 2。模块化插头的开发 并播放用于化学合成的硬件，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。这些目标将在五年内开发 在与NCAT的高度集成和协作的作案手术中。在1 - 2年中，我们将继续进行 通过制定规范，实施计划，原型，测试集成概念， 在3 - 5年内，NCAT的部署，集成和测试周期都将在此之后。通过发展 用于化学合成的操作编程语言，可以指定反应的要求 确切地说，我们将确保可编程化学（例如计算）可以在兼容上变得普遍 硬件。我们将开发的编程语言基于我们的化学描述语言χDL（1.0）， 这是开源。我们将介绍更强大的功能，例如循环以及何时条件 χDL（2.0）将等效于功能上的计算机编程语言，而不是用于 计算，χDL（2.0）将用于化学操作。此功能升级很重要，因为 语言将变得更加便携和普遍。这是因为语言不会依赖 外语不适合化学自动化。该系统将在格拉斯哥和NCAT上进行验证 使用涵盖有机化学跨度的一系列知名反应，并将涉及几种情况 研究表明如何编码新发现的化学。我们还将探索一系列 合成量表和使用最新状态的液液和固液提取系统的新方法 纯化和图书馆开发的膜技术。该系统将用于优化现有 化学反应和目标以及使用机器学习系统的新目标探索。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 结果将是新化学实体作为起点的识别，设计，合成和验证 用于制定新靶标的药物开发，以及用于药物筛查的化学空间的扩展。 项目将在NCAT和Glasgow领先，团队将与管理层共同协调 每个月将正式开会的团队，每周一次，每两周举行一次会议，每季度 评论。指导委员会将审查进度并向团队提供建议。