Effective Energy Functions for Proteins in Lipid Membranes

脂膜中蛋白质的有效能量函数

• 批准号: 0316667
• 负责人: Themis Lazaridis
• 金额: --
• 依托单位: CUNY City College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0316667&HistoricalAwards=false
• 关键词: Effective; Energy; Functions; Proteins; Lipid

The goal of this project is to develop an accurate and computationally efficient analytical implicit solvation model for membranes. An initial version of such a model (IMM1) has been recently proposed by extension of an implicit solvation model for aqueous proteins (EEF1). IMM1 predicts reasonable membrane insertion free energies, discriminates transmembrane from interfacially binding peptides, and gives stable molecular dynamics simulations of membrane proteins. This project aims to enhance the reliability and extend the applicability of IMM1 by testing some of its key assumptions and by incorporating several physical elements that are now missing. Specifically, this project involves: a. testing of the electrostatic screening model by comparison to continuum electrostatics calculations, b. extension to membrane proteins with an aqueous pore, such as porins or ion channels , c. addition of a separate lipid headgroup region with distinct solvent properties, d. incorporation of electrostatic effects arising from the dipole, surface, and transmembrane potentials, and e. calibration to available experimental data for quantitative prediction of binding free energies of peptides to membranes. The outcome of this work will be useful for understanding the energetic determinants of membrane protein structure, prediction of membrane protein structure from sequence, and studies of how conformational changes in membrane proteins are linked to their function. The models will be made available to the research community in both academia and the pharmaceutical industry. This research will be carried out at an institution where 60% of the students belong to underrepresented groups and undergraduates are heavily involved in research.

这个项目的目标是开发一个精确的和计算效率高的分析隐式溶剂化模型的膜。这种模型的初始版本（IMM 1）最近已被提出的水相蛋白质（EEF1）的隐式溶剂化模型的扩展。 IMM1预测合理的膜插入自由能，区分跨膜界面结合肽，并给出稳定的膜蛋白的分子动力学模拟。 该项目旨在通过测试IMM 1的一些关键假设并通过纳入目前缺失的几个物理元素来增强其可靠性并扩展其适用性。 具体而言，该项目包括：a. 通过与连续体静电学计算进行比较来测试静电屏蔽模型，B.延伸至具有水性孔的膜蛋白，例如孔蛋白或离子通道，c.添加具有不同溶剂性质的单独的脂质头基区，d.并入由偶极子、表面和跨膜电位引起的静电效应，以及e.校准可获得的实验数据，用于定量预测肽与膜的结合自由能。 这项工作的结果将有助于了解膜蛋白结构的能量决定因素，从序列预测膜蛋白结构，以及研究膜蛋白的构象变化与其功能的关系。 这些模型将提供给学术界和制药业的研究界。 这项研究将在一个60%的学生属于代表性不足的群体和本科生大量参与研究的机构进行。