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: 7955285
• 负责人: ROSALIE K CROUCH
• 金额: $ 0.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955285
• 关键词: Agonist; Binding; Binding Sites; Biochemical; Biomedical Computing; Blindness; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Eye diseases; Free Energy; Funding; Genetic; Grant; Human; Inherited; Institution; Ligand Binding; Ligands; Opsin; Proteins; Research; Research Personnel; Resources; Retinal Degeneration; Retinal Pigments; Route; Source; Specificity; United States National Institutes of Health; Vertebrate Photoreceptors; Vision; age related; design; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构为 中心，但不一定是研究者所在的机构。 (A)目标 视网膜变性是一个主要的遗传和年龄相关的原因，严重的眼病和失明。了解天然和合成的激动剂和拮抗剂与视色素的分子相互作用可以提供一种新的途径来阻止并可能逆转这种变性。 这项合作将利用网格支持的AutoLigand和AutoDock以及AutoDockTools来计算，1）表征人类视杆细胞和视锥细胞视蛋白的配体结合位点。2)预测已知激动剂和反向激动剂的结合模式和自由能，以及3）使用AutoDock Tools交互式Autoligand增强界面探索新的反向激动剂，以帮助设计具有更高效力和特异性的配体。 新的反向激动剂的功效将使用人视蛋白的生物化学研究来验证，以证明蛋白质配体相互作用。