COMPUTER SIMULATION OF AMPHIPHILIC AGGREGATES

提出了计算机模拟计算，以补充几个NIH 宾夕法尼亚大学目前正在进行的实验项目， 研究膜蛋白及其结构和功能。具体地说， 我们的目的是研究小蛋白与膜模拟物的结合， 底物，并试图研究膜结合部分的 在“现实”环境中的某些蛋白质。我们的一个系统 大脑由细胞色素c和自组装单层组成 （SAMs）由脂质分子组成。所讨论的地对空导弹将是 单层化学吸附到具有特定极性的固体基质上 端基（例如，NH 2），其静电结合细胞色素c。 另一个主题将涉及膜结合部分的结构 某些蛋白质（或小膜蛋白）及其性质 与宿主细胞膜的相互作用。初步研究将侧重于 磷脂单层和双层的真实建模， 通过真空MD研究对蛋白质片段的伴随研究。 最后一个目标是计算机模拟耦合膜- 蛋白质系统的数据，并与NMR数据进行比较。这些项目是合乎逻辑的 我们目前的NIH资助的研究计划的演变。两个新 本文还提出了一些倡议。第一个将尝试 表征常用麻醉气体与 α-螺旋蛋白。在这里，目标是详细了解 吸入麻醉剂如何以及在何处与蛋白质和其他细胞结合 组成人员。第二个涉及对“真实的”和 合成通道蛋白。后者旨在提供帮助 阐明并因此控制蛋白质功能的机制。在 总结，提出了最先进的计算机模拟计算 作为探索膜蛋白质某些基本方面的手段， 交互.为此，新的模拟代码和计算 毫无疑问，需要制定方法。远景目标 是为了补充我在宾夕法尼亚大学的同事们的实验项目： 教授医学院的达顿和埃肯霍夫教授以及布莱西和 Opelia在Dept。化学。

Computer simulation calculations are proposed to complement several NIH funded experimental programs currently underway at Penn that involve the study of membrane-proteins, their structure and function. Specifically, we aim to investigate the binding of small proteins to membrane mimetic substrates and to attempt studies of the membrane-bound portions of certain proteins in a 'realistic' environment. One system we have in mind consists of cytochrome c tethered to self-assembled monolayers (SAMs) composed of lipid molecules. The SAMs in question will be monolayers chemisorbed to a solid substrate with specific polar endgroups (e.g., NH2) that electrostatically bind the cytochrome c. Another theme will deal with the structure of membrane-bound portions of certain proteins (or small membrane proteins) and the nature of their interaction with the host membrane. Initial studies will focus on the realistic modeling of phospholipid monolayers and bilayers with concomitant investigation of the protein segments via vacuum MD studies. The final goal here is the computer simulation of a coupled membrane- protein system and comparison with NMR data. These projects are logical evolutions of our current NIH funded research program. Two new initiatives are also proposed herein. The first will attempt to characterize the interaction of commonly used anesthetic gases with alpha-helical proteins. Here, the goal is a detailed understanding of how and where inhalation anesthetics bind to proteins and other cellular constitutuents. The second involves modeling studies on both 'real' and synthetic channel proteins. The latter have been designed to help illucidate and hence control the mechanism of protein function. In summary, state-of-the-art computer simulation calculations are proposed as a means to probe certain fundamental aspects of membrane-protein interactions. To this end, new simulation codes and computational methodologies will undoubtedly need to be developed. The long-term goal is to complement the experimental programs of my colleagues at Penn: Profs. Dutton and Eckenhoff in the Medical School and Profs. Blasie and Opelia in the Dept. of Chemistry.