PRESERVING VISION IN INHERITED AND AGE-RELATED RETINAL DEGENERATIONS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 (A)目标 视网膜变性是严重眼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， 拮抗剂与视色素可以提供一种新的途径， 这种退化。 这项合作将利用支持网格的AutoLigand和AutoDock， 以及AutoDockTools进行计算，1）表征配体结合位点的 人视杆和视锥视蛋白。2)预测已知的结合模式和自由能 激动剂和反向激动剂; 3）使用AutoDock Tools探索新的反向激动剂 交互式Autoligand增强界面，帮助设计具有更高效力的配体， 的特异性 新的反向激动剂的疗效将通过生物化学研究进行验证 与人类视蛋白质的相互作用，以证明蛋白质配体相互作用。

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.