Benchmarks for Membrane Biophysics

膜生物物理学基准

• 批准号: 1713242
• 负责人: Roger Koeppe
• 金额: $ 71.75万
• 依托单位: University of Arkansas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1713242&HistoricalAwards=false
• 关键词: Benchmarks; Membrane; Biophysics

This project addresses fundamental gaps in our understanding of lipids and proteins in biological membranes. Biological function is governed by the molecular properties of proteins and other biomolecules that operate within the membrane micro-environment provided by and for living cells. As biological understanding progresses, computational methods are becoming increasingly important for predicting the properties of cell membranes. At the same time, the computational methods need to be checked and validated by means of experimental measurements that can serve as benchmarks for the calculations. This project provides such an experimental framework to serve as a basis for advancing the predictive power of computational biophysics. The overarching goal is to understand the operational diversity of membrane proteins for the performance and regulation of biological function. This project will sustain community outreach, dialogue, and early involvement of undergraduate students in cutting-edge research. This proposal will also expose young people to science and recruit them to engage in research through the "Science Café" program. This project addresses central issues in predictive membrane biophysics, including molecular orientation, dynamic properties and the ionization states of designated functional side chains of His, Lys, Glu, Asp and Arg in membrane proteins. The key methods involve peptide synthesis, stable isotope labeling, circular dichroism spectroscopy, solid-state magnetic resonance (NMR) measurements, and collaborations with computational biophysicists. The experimental approaches employ a novel "host" peptide design, developed by the investigators, in which minimal numbers of interfacial aromatic amino-acid residues serve to position a tilted transmembrane helix near a "tipping point" in lipid bilayer membranes. Within this context, the systematic incorporation of specific "guest" residues provides important insights concerning ionization behavior and protein-lipid molecular interactions that are essential for the biological functions of many classes of membrane proteins. The experimental results from this project are expected to establish fundamental benchmarks to aid the development and validation of computational methods for addressing the molecular mechanisms that govern the functioning of specific membrane proteins such as potassium channels, acetylcholine receptors or growth factor receptors, amongst others. This project is supported by the Molecular Biophysics Cluster of the Molecular and Cellular Biosciences Division in the Directorate for Biological Sciences.

这个项目解决了我们在理解生物膜中的脂质和蛋白质方面的根本差距。生物功能是由蛋白质和其他生物分子的分子性质决定的，这些分子在活细胞提供的和为活细胞提供的膜微环境中工作。随着生物学认识的进步，计算方法对于预测细胞膜的性质正变得越来越重要。同时，需要通过可作为计算基准的实验测量来检查和验证计算方法。该项目提供了这样一个实验框架，作为提高计算生物物理学预测能力的基础。首要目标是了解膜蛋白的操作多样性，以实现和调节生物功能。该项目将支持社区外展、对话和本科生早期参与前沿研究。这项提议还将使年轻人接触科学，并通过“科学咖啡馆”计划招募他们从事研究。该项目致力于预测膜生物物理的中心问题，包括膜蛋白中His、Lys、Glu、Asp和Arg的分子取向、动力学性质和指定功能侧链的电离状态。关键方法包括多肽合成、稳定同位素标记、圆二色谱、固体核磁共振测量以及与计算生物物理学家的合作。实验方法采用了一种由研究人员开发的新的“宿主”多肽设计，其中最少的界面芳香氨基酸残基用于将倾斜的跨膜螺旋定位在脂质双层膜的“引爆点”附近。在这种背景下，系统地结合特定的“客体”残基提供了关于电离行为和蛋白质-脂质分子相互作用的重要见解，这些行为和分子相互作用对于许多类别的膜蛋白的生物功能是必不可少的。该项目的实验结果有望建立基本的基准，以帮助开发和验证计算方法，以解决控制特定膜蛋白功能的分子机制，如钾通道、乙酰胆碱受体或生长因子受体等。该项目得到了生物科学局分子和细胞生物科学司分子生物物理组的支持。

项目成果

Influence of interfacial tryptophan residues on an arginine-flanked transmembrane helix

界面色氨酸残基对精氨酸侧翼跨膜螺旋的影响

• DOI: 10.1016/j.bbamem.2019.183134
• 发表时间: 2020
• 期刊: Biochimica et Biophysica Acta (BBA
• 作者: Sustich, Sara J.;Afrose, Fahmida;Greathouse, Denise V.;Koeppe, Roger E.
• 通讯作者: Koeppe, Roger E.

Membrane Bending Moduli of Coexisting Liquid Phases Containing Transmembrane Peptide.

• DOI: 10.1016/j.bpj.2018.03.026
• 发表时间: 2018-05
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: R. D. Usery;T. A. Enoki;S. Wickramasinghe;V. Nguyen;David G. Ackerman;D. Greathouse;R. Koeppe;F. Barrera;G. Feigenson

Examination of pH dependency and orientation differences of membrane spanning alpha helices carrying a single or pair of buried histidine residues

• DOI: 10.1016/j.bbamem.2020.183501
• 发表时间: 2021-01-01
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
• 影响因子: 3.4
• 作者: Afrose, Fahmida;Martfeld, Ashley N.;Koeppe, Roger E., II
• 通讯作者: Koeppe, Roger E., II

Wavelength-Selective Fluorescence of a Model Transmembrane Peptide: Constrained Dynamics of Interfacial Tryptophan Anchors

模型跨膜肽的波长选择性荧光：界面色氨酸锚的约束动力学

• DOI: 10.1007/s10895-018-2293-5
• 发表时间: 2018
• 期刊: Journal of Fluorescence
• 影响因子: 2.7
• 作者: Pal, Sreetama;Koeppe, Roger E.;Chattopadhyay, Amitabha
• 通讯作者: Chattopadhyay, Amitabha

Flanking aromatic residue competition influences transmembrane peptide helix dynamics

• DOI: 10.1002/1873-3468.13926
• 发表时间: 2020-09
• 期刊: FEBS Letters
• 影响因子: 3.5
• 作者: M. McKay;D. Greathouse;R. Koeppe