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

乙酰胆碱受体是负责神经系统电活动的一大类膜蛋白的代表。这种受体参与了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促进我们对这些重要生物分子的理解。Gund博士建议为CYBER 205矢量超级计算机开发一种计算方法，系统地调查具有多种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分子动力学计算中实时传递信息到基于VAX的分子建模系统，以进一步进行交互操作。其他目标包括将从头算和分子力学计算的信息传递到基于VAX的分子建模系统。这些目标的应用将是确定包括多肽在内的胆碱能配体的生物活性构象，受体定位，计算受体-配体结合和非结合复合物的构象状态，以及设计新的配体，以探索受体-配体结合的地形和机制。

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.