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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 (一) 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。了解天然和合成激动剂的分子相互作用 视觉色素的拮抗剂可以提供一条新的途径来停止和可能逆转 这样的退化。 此次合作将利用支持网格的 AutoLigand 和 AutoDock， 以及 AutoDockTools 进行计算，1) 表征配体结合位点 人类视杆细胞和视锥细胞视蛋白。 2）预测已知的结合模式和自由能 激动剂和反激动剂，3) 使用 AutoDock 工具探索新的反激动剂 交互式 Autoligand 增强界面可帮助设计具有更高效力的配体 特异性。 新反向激动剂的功效将通过生化研究进行验证 与人视蛋白一起证明蛋白质配体相互作用。