VORONOI MAPPING OF COCAINE RECEPTORS

关于可卡因生物作用的药理学研究已经确定， 中枢神经系统中的几个特异性结合位点 具有毒性、自我给药行为和药物的其他特征 虐待有体外试验显示与生理学相关性良好， 效应，实验者据此测量了特异性结合常数 一系列可卡因衍生物的中枢神经系统受体。以来 这些测定通常用脑匀浆进行， 很可能是膜结合蛋白质，因此， 受体的X射线晶体结构，我们必须用 绑定数据。我们能不能用这些有限的信息推断出一个详细的图片- 受体位点的形状和药物-受体的能量学 互动？能推断出多少细节？我们能学到什么， 实际上涉及不止一种受体这些信息可以 用于提示可卡因拮抗剂或对以下药物具有更大特异性的药物： 特定的受体？我们建议加强我们严格的计算机算法 用于受体定位，并将其应用于现有的实验数据， 可卡因与中枢神经系统受体的结合，以回答这些问题。

Pharmacological studies on the biological action of cocaine have identified several sites of specific binding in the central nervous system associated with toxicity, self administration behavior, and other features of drug abuse. There are in vitro assays showing good correlation with physiologica effects, whereby experimentalists have measured specific binding constants to well-defined CNS receptors for a series of cocaine derivatives. Since these assays are typically done with brain homogenates, and the receptors are probably membrane bound proteins, there is little hope for a detailed X-ray crystal structure of the receptor, and we must make do with just the binding data. Can we use this limited information to deduce a detailed pic- ture of the shape of the receptor site and the energetics of drug-receptor interactions? How much detail can be deduced? What can we learn if the assa actually involves more than one type of receptor? Can this information be used to suggest cocaine antagonists or drugs with greater specificity for particular receptors? We propose to enhance our rigorous computer algorithm for receptor mapping and apply them to the available experimental data on cocaine binding to CNS receptors, in order to answer these questions.