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

乙酰胆碱受体是一大类 膜蛋白负责的电活动， 神经系统 该受体参与了许多 生物学上重要的过程，如睡眠的调节， 记忆和学习过程。 了解结构和 受体的功能以及能够预测活性 配体将大大促进我们对这些重要的 生物分子 冈德博士建议开发一种计算方法， 大分子构象系统研究 CYBER 205具有许多构象自由度 向量超级计算机 然后她会把来自 构象计算以及分子动力学 计算CYBER在真实的时间，以VAX为基础的分子 为进一步的交互式操作建模系统。其他 目标将涉及从头开始传递信息， 基于VAX的分子力学计算 建模系统 这些目标的应用将是确定 胆碱能配体的生物活性构象，包括 多肽，受体作图，构象计算 受体-配体结合和未结合复合物的状态，以及 设计新的配体，探索地形， 受体-配体结合机制。

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.