Mos. Gund Techniques to Search Confor ational Space for Cholinergic Ligands

莫斯。

• 批准号: 8619490
• 负责人: Tamara Gund
• 金额: --
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8619490&HistoricalAwards=false
• 关键词: Mos.; Gund; Techniques; Search; Confor

The acetylcholine receptor is a representative of a large class of membrane proteins responsible for the electrical activity of the nervous system. The receptor is involved in many biologically important processes, such as regulation of sleep, memory and learning processes. Understanding the structure and function of the receptor as well as being able to predict active ligands will greatly further our understanding of these important biological molecules. Dr. Gund proposes to develop a computational method to systematically survey molecular conformations for large molecules with many degrees of conformational freedom for the CYBER 205 vector supercomputer. She will then relay information from the conformational calculations as well as from molecular dynamics calculations on the CYBER in real time to a VAX based molecular modeling system for further interactive manipulations. Other objectives will involve relaying information from ab initio and molecular mechanics calculations to a VAX based molecular modeling system. The applications of these objectives will be to determine the bioactive conformations of cholinergic ligands including polypeptides, receptor mapping, calculation of conformational states of receptor-ligand bound and unbound complexes, and design of new ligands which would explore the topography and mechanism of receptor-ligand binding.

乙酰胆碱受体是一大类膜蛋白的代表，负责神经系统的电活动。该受体参与许多重要的生物学过程，如睡眠、记忆和学习过程的调节。了解受体的结构和功能以及能够预测活性配体将极大地加深我们对这些重要生物分子的理解。冈德博士建议开发一种计算方法，为Cyber 205向量超级计算机系统地测量具有多个构象自由度的大分子的分子构象。然后，她将从构象计算以及来自网络上的分子动力学计算的信息实时传递到基于VAX的分子建模系统，以进行进一步的交互操作。其他目标将包括将从头计算和分子力学计算的信息传递到基于VAX的分子建模系统。这些目标的应用将包括确定胆碱能配体的生物活性构象，包括多肽、受体定位、受体-配体结合和非结合复合体的构象计算，以及探索受体-配体结合的形貌和机制的新配体的设计。