Identifying Genetic Contributions to Adverse Drug Reactions

确定遗传因素对药物不良反应的影响 项目摘要 将创建生物信息学工具，以便于搜索基因组中可以阐明以前的变异 无法解释的药物不良反应（ADR）。已知的药物靶蛋白仅代表少数几个 这是药物设计和寻找基因解释的一个错失的机会， ADR。我们正在寻求创建新的生物信息学工具，用于识别 药物及其代谢物。我们的目标是建立工具，帮助确定潜在的遗传原因 罕见和无法解释的ADR，因此可以避免这些影响。我们最初的重点将是现有的非常大的 关于遗传变异和药物不良反应的数据集，这些数据集目前没有联系，以确定可能的新联系 在数据集之间。第一个具体目标是使用最好的可用蛋白质创建对接服务器 结构，使任何蛋白质的变体都可以用于对接研究，并作为可能的来源进行检查。 副作用扩展到黑暗基因组中第二个具体目标是创建在线工具， 特异性ADR并产生药物的三维结构和药物代谢产物，为对接做好准备 研究并创建快速筛选工具。研究人员可以使用这些工具来优先考虑药物蛋白质 用于进一步的计算机模拟或体外研究。这些工具将有助于快速检验关于以下方面的假设： 在现有的药物和正在设计的药物中，有害药物副作用的分子原因， 这是消除ADR和设计更有效药物的一步。

Identifying Genetic Contributions to Adverse Drug Reactions Project Summary Bioinformatics tools will be created that facilitate searching the genome for variants that can elucidate previously unexplained adverse drug reactions (ADRs). Known protein targets for pharmaceuticals represent only a few percent of the genome and this is a missed opportunity in drug design and in finding genetic explanations for ADRs. We are seeking to create new bioinformatics tools for identifying the off-target binding sites of pharmaceuticals and their metabolites. Our goal is to build tools that help identify the underlying genetic causes of rare and unexplained ADRs so these effects can be avoided. Our initial focus will be on very large existing data sets on genetic variation and on ADRs that are currently not linked to identify possible new connections between the datasets. The first specific aim is to create a docking server using the best available protein structures so that variants of any protein can be used in docking studies and be examined as a source of possible side effects expanding into the dark genome. The second specific aim is to create online tools that identify specific ADRs and produce the three-dimensional structures of drugs and drug metabolites prepared for docking studies and create fast screening tools. Together these tools can be used by researchers to prioritize drug protein interactions for further in silico or in vitro studies. These tools will facilitate rapid testing of hypotheses about molecular causes of harmful drug side effects in both available drugs and drugs being designed today, a critical step toward eliminating ADRs and designing more effective drugs.