Fragment-Screen: From fragments to high affinity binders interfacing integrated structural biology, medicinal chemistry and artificial intelligence

片段筛选将为基于片段的药物发现(FBDD)开发创新的仪器、工作流程以及实验和计算方法，使所有生物靶标以及工业界和学术界的科学家能够获得基于结构的早期药物发现。建立的工作流程将使用结构生物学见解和相关数据来支持人工智能(AI)方法，以指导药物开发中的药物化学。Fragment-Screen汇集了来自四个ESFRI里程碑研究基础设施(RIS)的科学家：ESRF(欧洲同步加速器)和分布式RIS EU-OPENSCREEN Eric(药物化学)，ELIXIR(生命科学数据资源)，在Indict-Eric(集成结构生物学)的协调下，以及包括中小企业在内的科学仪器、计算和人工智能领域的七个行业合作伙伴，以消除早期药物发现中的关键瓶颈。新的仪器和工作流程将在欧洲RIS上提供，而新的仪器将进行商业化，以增加欧洲工业在药物设计方面的技术竞争力，以及结构生物学RIS对制药和生物技术行业的吸引力。片段筛选将在早期药物发现中实施开放的科学方法，以最大限度地发挥筛选活动的影响。生成的数据将可供访问，以便应用人工智能的迭代周期将改善药物发现的响应时间。我们将为药物设计中人工智能的客观和独立评估创建一个框架，以确定这一蓬勃发展的研究领域的关键发展。将通过示范性和试验性研究建立严格交叉验证的方法，结果将传播给附属于欧洲RIS及其他机构的大型科学界。

Fragment-Screen will develop innovative instrumentation, workflows and experimental and computational methodologies for fragmentbased drug discovery (FBDD) enabling access to early phase structure-based drug discovery for all biological targets and for scientists both in industry and academia. The established workflows will use structural biology insights and associated data to feed artificial intelligence (AI) methodology to guide medicinal chemistry in drug development. Fragment-Screen brings together scientists from four ESFRI Landmark research infrastructures (RIs): ESRF (the European synchrotron) and the distributed RIs EU-OPENSCREEN ERIC (medicinal chemistry), ELIXIR (data resources for life science) under the coordination of Instruct-ERIC (integrated structural biology) and seven industry partners in scientific instrumentation and computational and AI sectors including SMEs to remove crucial bottlenecks in early phase drug discovery. The new instrumentation and workflows will be available at European RIs, while the new instruments will be commercialised to increase the technological competitiveness of European industry in drug design and the attractiveness of structural biology RIs for the pharmaceutical and biotech sectors. Fragment-Screen will implement open science approaches in early drug discovery to maximise the impact of screening campaigns. Generated data will be made accessible so that iterative cycles applying AI will improve response times for drug discovery. We will create a framework for the objective and independent evaluation of AI in drug design to identify critical developments in this thriving research field. Methodologies for rigorous cross-validation will be established through demonstrator and pilot studies and results will be disseminated to the large scientific communities affiliated to the European RIs and beyond.