PRESERVING VISION IN INHERITED AND AGE-RELATED RETINAL DEGENERATIONS

保护遗传性和年龄相关性视网膜变性患者的视力

• 批准号: 8362798
• 负责人: ARTHUR J. OLSON
• 金额: $ 3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362798
• 关键词: Agonist; Binding; Binding Sites; Biochemical; Biomedical Computing; Blindness; Collaborations; Eye diseases; Free Energy; Funding; Genetic; Grant; Human; Inherited; Ligand Binding; Ligands; National Center for Research Resources; Opsin; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Retinal Degeneration; Retinal Pigments; Route; Source; Specificity; United States National Institutes of Health; Vertebrate Photoreceptors; Vision; age related; cost; design; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. (A) OBJECTIVES Retinal degeneration is a major genetic and age related cause of serious eye disease and blindness. Understanding the molecular interactions of natural and synthetic agonists and antagonists with the visual pigments can provide a new route to halting and possibly reversing such degeneration. This collaboration will utilize grid-enabled AutoLigand and AutoDock, as well as AutoDockTools to computationally, 1) characterize the ligand binding sites of the human rod and cone opsin proteins. 2) predict the binding modes and free energies of known agonists and inverse agonists and 3) explore new inverse agonists using AutoDock Tools interactive Autoligand enhanced interface to help design ligands with increased potency and specificity. The efficacy of the new inverse agonists will be validated using biochemical studies with the human opsin proteins to demonstrate protein ligand interactions.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 （a）目标 视网膜变性是严重眼部疾病的主要遗传和年龄相关原因 失明。了解自然和合成激动剂的分子相互作用以及 带有视觉颜料的对手可以提供新的停止途径，并可能逆转 这样的变性。 这项合作将利用启用网格的自动配置和自动售货机，作为 以及按计算上的自动库托工具，1）表征该配体结合位点 人棒和锥蛋白蛋白。 2）预测已知的结合模式和自由能 激动剂和反向激动剂以及3）使用Autodock工具探索新的反激动剂 交互式自动配置增强界面，以帮助设计配体的效力增加和 特异性。 新的反激动剂的功效将通过生化研究验证 用人蛋白蛋白展示蛋白配体相互作用。