PRESERVING VISION IN INHERITED AND AGE-RELATED RETINAL DEGENERATIONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 (A)目标 视网膜变性是导致严重眼病和失明的主要遗传和年龄相关原因。了解天然和合成的激动剂和拮抗剂与视觉色素的分子相互作用可以提供一条阻止并可能逆转这种退化的新途径。这项合作将利用网格启用的AutoLigand和AutoDock以及AutoDockTools来计算：1)表征人类视杆蛋白和视锥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；3)利用AutoDock工具的交互式自动配基增强界面，开发新的反向激动剂，以帮助设计具有更高效力和特异性的配体。新的反向激动剂的有效性将通过对人类视蛋白的生化研究来验证，以证明蛋白质配体的相互作用。

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.