NIDA Center of Excellence OF Computational Drug Abuse Research (CDAR)

描述（由申请人提供）： 我们建议在匹兹堡大学（皮特）和（CMU）之间建立一个NIDA计算药物滥用研究卓越中心（CDAR），其目标是推进和确保最先进的计算技术的生产和广泛使用，这将促进和加强药物滥用（DA）研究，无论是在当地（匹兹堡）地区还是全国范围内。为此，我们将开发/集成工具DA域特定的化学-蛋白质-基因组学映射使用化学信息学，计算生物学和计算基因组学方法，通过集中计算化学基因组学（或化学基因组学）资源，同时也使它们在云服务器上可用。该中心将通过以下研究支持核心促进合作和推进基于知识的转化研究，并提高正在进行的资助研究项目（FRP）的有效性：（1）DA计算化学基因组学核心（CC 4DA）将通过开发新的化学基因组学工具和汇编收集/生成的数据沿着其他核心的数据，帮助解决多种药物成瘾/多种药理学问题，进入一个DA知识为基础的化学基因组学（DA-KB）库，将访问DA社区。(2)计算生物学核心（CB 4DA）将专注于开发一种资源，用于对DA物质及其靶蛋白之间的相互作用进行基于结构的研究，以及评估参与DA和成瘾的受体和转运蛋白的可药性。这些活动将通过定量系统药理学方法进行补充，以实现DA研究的系统级方法。(3)计算基因组学核心（CG 4DA）将使用开发的机器学习模型和算法在全基因组范围内发现新的DA靶点、标记和表观遗传影响。(4)行政核心将协调中心的活动，提供管理，以监督CDAR活动与科学指导委员会（SSC）和外部咨询委员会（EAB）协商，确保软件/数据在核心和FRP之间的有效传播，并建立指导机制以培训初级研究人员。总体而言，该中心将努力实现将计算化学，生物学和基因组学的进步转化为新型个性化DA治疗方法的长期目标。

DESCRIPTION (provided by applicant): We propose to establish a NIDA Center of Excellence for Computational Drug Abuse Research (CDAR) between the University of Pittsburgh (Pitt) and (CMU), with the goal of advancing and ensuring the productive and broad usage of state-of-the-art computational technologies that will facilitate and enhance drug abuse (DA) research, both in the local (Pittsburgh) area and nationwide. To this end, we will develop/integrate tools for DA-domain-specific chemical-to-protein-to-genomics mapping using cheminformatics, computational biology and computational genomics methods by centralizing computational chemical genomics (or chemogenomics) resources while also making them available on a cloud server. The Center will foster collaboration and advance knowledge-based translational research and increase the effectiveness of ongoing funded research project (FRPs) via the following Research Support Cores: (1) The Computational Chemogenomics Core for DA (CC4DA) will help address polydrug addiction/polypharmacology by developing new chemogenomics tools and by compiling the data collected/generated, along with those from other Cores, into a DA knowledge-based chemogenomics (DA-KB) repository that will be made accessible to the DA community. (2) The Computational Biology Core (CB4DA) will focus on developing a resource for structure-based investigation of the interactions among substances of DA and their target proteins, in addition to assessing the drugability of receptors and transporters involved in DA and addiction. These activities will be complemented by quantitative systems pharmacology methods to enable a systems-level approach to DA research. (3) The Computational Genomics Core (CG4DA) will carry out genome-wide discovery of new DA targets, markers, and epigenetic influences using developed machine learning models and algorithms. (4) The Administrative Core will coordinate Center activities, provide management to oversee the CDAR activities in consultation with the Scientific Steering Committee (SSC) and an External Advisory Board (EAB), ensure the effective dissemination of software/data among the Cores and the FRPs, and establish mentoring mechanisms to train junior researchers. Overall, the Center will strive to achieve the long-term goal of translating advances in computational chemistry, biology and genomics toward the development of novel personalized DA therapeutics.