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.

项目概要 在这个合作项目中，我们将开发一个用于化学反应自动化和执行的系统 这项工作将跨越一系列硬件和规模来合成已知和未知分子。 利用我们实验室过去 6 年在 Chemputer（一种可编程化学合成 机器人）和化学计算原理（化学合成以一种化学物质表达的概念） 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. 开发 将运行合成协议的化学编程语言标准； 2. 模块化插件的开发； 并运行化学合成硬件，包括与第三方系统的接口 3. 创建反应； 化学合成和发现的筛选系统将在五年内开发。 在第 1-2 年中，我们将与 NCATS 采取高度集成和协作的工作方式。 通过制定规范、实施计划、原型、测试集成概念来实现所有三个具体目标， 随后，在第 3-5 年，将在 NCATS 进行部署、集成和测试周期。 一种用于化学合成的操作编程语言，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，可以在兼容的 我们将开发的编程语言基于我们的化学描述语言 χDL (1.0)， 这是开源的。我们将引入更强大的函数，例如 for 循环和 if when 条件，以便 χDL (2.0) 将相当于一种函数式计算机编程语言，但不用于 计算，χDL (2.0) 将用于化学操作，这种功能升级非常重要，因为 语言将变得更加可移植和通用，这是因为语言将不再依赖于。 不适合化学自动化的外部语言 该系统将在格拉斯哥和 NCATS 进行验证。 使用一系列涵盖有机化学跨度的众所周知的反应，并将涉及多个案例 研究展示了如何对新发现的化学物质进行编码。我们还将探索一系列的研究。 使用最先进技术的液-液和固-液萃取系统的合成规模和新方法 该系统将用于优化现有的纯化和文库开发。 化学反应和目标，以及使用机器学习系统探索新目标。 分析软件系统桥将包括 NMR、IR、MS 和 HPLC，以提供该项目的实时反馈。 结果将以新化学实体的识别、设计、合成和验证为起点 用于新靶点的药物开发，以及扩大可用于药物筛选的化学空间。 该项目将由 NCATS 和格拉斯哥牵头，各团队将与管理层共同协调 团队每月都会举行正式会议，每周和每两周举行一次频繁的会议，每季度举行一次 指导委员会将审查进展情况并向团队提供建议。