HIGH RESOLUTION X-RAY STUDIES OF OPIATES AND RECEPTORS MAPPING

拟议研究的目标是绘制鸦片类药物的MU图。 受体。将采取两种方法：一种是X射线结构 受体活性药物分子的测定 二是用计算机模拟受体部位 模拟。在第一种方法中，X射线结晶学方法 将被用来确定几何结构、电子密度 分子静电势分布(EDD)和分子静电势(MEP) 药物分子，包括纳洛酮、吗啡、美沙酮 以及他们的衍生品。使用锁和钥匙的概念 配体-受体结合的机制，活性部位将是 基于与这些配体互补的结构进行建模 分子。大量的数据已经存在于 研究人员先前和正在进行的关于配体的研究 分子。关于受体建模的试验程序已经被 写成与这些分子的几何形状相适应的表面，并 改进和开发用于模拟的计算机程序 感受器位置。

The objective of the proposed research is to map the opiate mu receptor. Two approaches will be taken: one is X-ray structure determination of drug molecules that are active at the receptor site, and the second is receptor site modeling by computer simulation. In the first approach, X-ray crystallographic methods will be used to determine the geometry, electron density distribution (EDD) and molecular electrostatic potential (MEP) of the drug molecules, which include naloxone, morphine, methadone and their derivatives. Using the concept of lock-and-key mechanism of ligand-receptor binding, the active site will be modeled based on a structure complementary to these ligand molecules. Considerable data already exist from the investigator's previous and ongoing studies on the ligand molecules. A trial program on the receptor modeling has been written to fit surfaces to the geometry of these molecules, and to improve and develop the computer program for the modeling of the receptor site.