Computational Core

项目摘要/摘要-计算核心 我们建议成立生物医学卓越研究中心(COBRE)进行药物研究 肯塔基大学(英国)的创新与研究。CPRI将作为一个综合性的多学科中心 侧重于翻译化学生物学[化学生物学的纽带(化学生物学的应用 开发有效的探针/模型以促进我们对生物学的理解的原则)和药学 科学(将药学原理应用于解决未满足的问题的先进引线/材料/装置 临床需求)]。科布雷将利用和开发独特的翻译化学生物学研究支持 基础设施/专业知识，以促进初级教师指导和职业发展，创新的生物医学 研究探索/工具/模型/材料的开发和验证，以及潜力的早期进展 “可转换”资产。在此背景下，由詹昌国博士指导的CPRI计算核心将 利用独特的计算专业知识、商业和内部软件/方法以及英国强大的 支持一系列计算服务的计算处理网络，以推进Cobre项目和 试点目标。核心将提供为项目/试点需求量身定制的服务，以促进 开发新的假设/模型，并简化实验研究的优先顺序。具体来说， 核心将实现对大分子靶标和靶标-配体复合体的分子建模/模拟， ADMET预测研究，基于结构的虚拟筛选配基发现，从头开始配基设计，以及 基于人工智能的方法。这套服务经过战略性设计，可与 互补，CPRI翻译核心和CPRI附属Cobre为分子提供的支持 药物有机合成核心。总体而言，CPRI相应的完全集成的研究支持套件 能力和专业知识将加快创新的临床前转化研究，并促进初级 调查员的职业发展。

PROJECT SUMMARY/ABSTRACT – COMPUTATIONAL CORE We propose to establish a Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation at the University of Kentucky (UK). CPRI will serve as a comprehensive multidisciplinary center focused on translational chemical biology [the nexus of chemical biology (the application of chemical biology principles to develop validated probe/models to advance our understanding of biology) and pharmaceutical science (the application of pharmaceutical principles to advance leads/materials/devices that address unmet clinical needs)]. The COBRE will leverage and develop unique translational chemical biology research support infrastructure/expertise to facilitate junior faculty mentorship and career development, innovative biomedical research probe/tool/model/materials development and validation, and the early advancement of potential ‘translatable’ assets. Within this context, the CPRI Computational Core, directed by Dr. Chang-Guo Zhan, will leverage unique computational expertise, commercial and in-house software/methods, and UK’s formidable computational processing network to support a range of computational services to advance COBRE project and pilot objectives. The Core will provide services individually tailored to project/pilot needs that facilitate the development of new hypotheses/models and streamline the prioritization of experimental studies. Specifically, the Core will enable molecular modeling/simulation of macromolecular targets and target-ligand complexes, ADMET prediction studies, structure-based virtual screening for ligand discovery, de novo ligand design, and artificial intelligence-based methods. This suite of services has been strategically designed to integrate with, and complement, the support provided by the CPRI Translational Core and the CPRI-affiliated COBRE for Molecular Medicine Organic Synthesis Core. Together, CPRI’s corresponding fully integrated suite of research support capabilities and expertise will accelerate innovative preclinical translational research and facilitate junior investigator career development.