INTERACTION OF INHALATIONAL ANESTHETICS WITH MACROMOLECU

由Roderick G博士领导。埃肯霍夫，调查人员建议检查 吸入麻醉药与氟烷的结合作用 特别是简单蛋白质和脂质分子也被选择 定义的模型。主要目的是确定结构和 麻醉剂与这些模型系统结合的动态后果， 了解麻醉剂结合部位的性质和一般的 麻醉剂结合相对于蛋白质构象的后果。 该计划项目包括三个实验部分，一个 一个专门用于分子建模的组件， 该计划所需的肽的合成，以及适度的行政管理 核心 项目I（Dr. Roderick G. Eckenhoff）将描述范围和 麻醉剂与简单肽、脂质和脂肽结合的位置 系统.光亲和标记方法将用于研究低亲和力 结构，以及纯的以及含蛋白质的脂质双层。项目 II（Jonas Johannson博士）将检查麻醉分配到各种 有机溶剂，并使用此信息来设计和分析更多 复杂的，四个α-螺旋束相对于构象和 麻醉剂结合的动态后果。项目III（Dr. Paul A. Liebman）将专注于更大的蛋白质分子，包括异三聚体 GTP结合蛋白与麻醉剂的结合及其对 折叠稳定性和功能。项目四（Michael A.克莱因）将使用 计算机模拟，以实现这些定量的理解 分子水平上的系统。分子动力学模拟将是 应用于将氟烷和异氟烷分配到模型溶剂中， 这些麻醉剂与模型肽，脂膜， 和离子通道。

Led by Dr. Roderick G. Eckenhoff, the investigators propose to examine the binding interactions of inhalational anesthetics in general and halothane in particular with simple protein and lipid molecules chosen as well defined models. The main objective is to determine the structural and dynamic consequences of anesthetic binding to these model systems in order to understand the nature of anesthetic binding sites and the general consequences of anesthetic binding with respect to protein conformation. The program project consists of three experimental components, one component dedicated to molecular modeling, a core facility for the synthesis of peptides required by the program, and a modest administrative core. Project I (Dr. Roderick G. Eckenhoff) will characterize the extent and location of anesthetic binding to simple peptide, lipid, and lipid-peptide systems. Photoaffinity labeling methods will be used to study low affinity structure, and pure as well as protein containing lipid bilayers. Project II (Dr. Jonas Johannson) will examine anesthetic partition into various organic solvents and use this information to design and assay more complex, four-alpha-helix bundles with respect to the conformational and dynamic consequences of anesthetic binding. Project III (Dr. Paul A. Liebman) will focus on larger protein molecules, including heterotrimeric GTP binding proteins with respect to anesthetic binding and its effects on folding stability and function. Project IV (Dr. Michael A. Klein) will use computer simulations to achieve a quantitative understanding of these systems at the molecular level. Molecular dynamic simulations will be applied to the partition of halothane and isoflurane into model solvents, the interaction of these anesthetics with model peptides, lipid membranes, and ion channels in lipid membranes.