μ-芋螺毒素电子结构与构效关系研究  

Studies on electronic structure and structure-activity relationship ofμ-conotoxin

作　　者：胡亚兰[1] 黄锋[1] 蒋辉[1] 范崇旭[1] 丁晓琴[1] 陈常英[1] 陈冀胜[1] 

机构地区：[1]北京药物化学研究所,北京102205

出　　处：《计算机与应用化学》2006年第5期403-406,共4页Computers and Applied Chemistry

摘　　要：探讨μ-芋螺毒素的活性部位、作用方式及结构-活性关系,讨论μ-芋螺毒素同肌肉型钠通道受体的相互作用特点。采用AMl方法对μ-芋螺毒素的代表物μ-GIIIA整体分子进行量子化学计算。研究结果表明分布于μ-GIIIA分子笼形结构表明突出部位的几个极性氨基酸如Arg^(13)、Arg^(19)、Arg^1、Lys^(11)、Lys^(16)等是主要的正电荷区域,在与受体结合时是接受电子的主要部位；Hyp^(17)、Asp^(12)等为主要的负电荷区域,为供电子的主要部位。通过与经典的钠通道拮抗剂比较,发现在μ-GIIIA(肌肉型钠通道拮抗剂)中,相近的极性氨基酸侧链之间正负电荷部位的距离为8(?),而神经型钠通道拮抗剂正负电荷部位之间的距离为4(?)作用,从而解释了这两种钠通道拮抗剂与不同受体亚型作用的原因,并由此探讨了这两种受体亚型的不同的电子结构特征。To study μ-conotoxin features of electronic structure, active sites, mechanism of action and structure-activity relationship, discuss features of interaction between μ-conotoxins and receptors in muscle-type sodium channels on the bases of electronic and spatial structure. The quantum chemical calculation for whole μ-conotoxin GIIIA has been undertaken by AMI. Various information of electronic structure was obtained. The study of the results showed that some polar amino acids such as Asp^13 , Lys^11 , Lys^16 , Arg^19 , Arg^1 and Asp^12 , Hyp^17 acts as electronic acceptors and donor respectively, these amino acids are all situated in the projecting sites of the surface of cage-shape structure of the molecule. The μ-conotoxin GIIIA was compared with classical sodium channel blockers such as TTX and STX, it was found that among the side chains of polar amino acids which are near to each other the distance between positive and negative charge sites is about 8A for μ-conotoxin GIIIA （muscle-type sodium channel blocker） , but in neuron-type sodium channel blockers the distances between positive and negative charge sites is about 4A. Thus it explained that the two type of sodium channel blocker interacts with the different subtypes. Further, different features of electronic structures have also been discussed for the two subtypes of the sodium channels receptor.

关 键 词：μ-芋螺毒素 量子化学计算 电子结构 空间结构 构效关系 

分 类 号：O641.121[理学—物理化学] O641.122[理学—化学]