Identifying Genetic Contributions to Adverse Drug Reactions

确定药物不良反应的遗传因素 项目摘要 生物信息学工具将被创建，以促进搜索基因组中先前可以阐明的变异 不明原因的药物不良反应(ADRs)。已知的药物蛋白质靶点仅代表少数几个 %的基因组，这是药物设计和寻找基因解释的机会 不良反应。我们正在寻求创造新的生物信息学工具来识别脱靶结合位点 药物及其代谢物。我们的目标是建立帮助识别潜在遗传原因的工具 罕见和无法解释的不良反应的发生，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 关于遗传变异和目前尚未关联的ADR的数据集，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一个对接服务器 结构，使任何蛋白质的变体可以用于对接研究，并作为可能的来源进行检查 副作用扩展到黑暗基因组。第二个具体目标是创建在线工具，以识别 用于对接的药物和药物代谢物的三维结构 研究和开发快速筛查工具。结合这些工具，研究人员可以用来确定药物蛋白质的优先顺序 相互作用，以进一步在硅胶或体外研究。这些工具将促进对以下假设的快速测试 现有药物和目前正在设计的药物中有害药物副作用的分子原因，一个关键的 朝着消除不良反应和设计更有效的药物迈进一步。

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.