Membrane Protein Stability

膜蛋白稳定性

• 批准号: 10295197
• 负责人: Karen G. Fleming
• 金额: $ 36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10295197
• 关键词: Address; Affect; Bacteria; Binding; Biological; Biological Assay; Biological Models; Biology; Catalysis; Client; Complement; Complex; Computational algorithm; Computer Models; Coupling; Data; Data Reporting; Databases; Deuterium; Disease; Disulfides; Engineering; Environment; Enzymes; Equilibrium; Foundations; Fractionation; Free Energy; Human body; Hydrogen; Hydrogen Bonding; Hydrophobicity; Integral Membrane Protein; Investigation; Kinetics; Knowledge; Laboratories; Lateral; Lipid Bilayers; Lipids; Location; Mathematics; Measurement; Measures; Membrane; Membrane Proteins; Modeling; Molecular; Mutation; Organic solvent product; Pharmaceutical Preparations; Phospholipids; Physical Chemistry; Positioning Attribute; Protein Engineering; Proteins; Regulation; Research; Scaffolding Protein; Side; Site; Solvents; Sorting - Cell Movement; Specific qualifier value; Structure; Techniques; Testing; Therapeutic; Thermodynamics; Training; Vertebral column; Water; Work; base; biophysical analysis; biophysical tools; chemical group; combat; design; driving force; experimental study; in vivo; interfacial; microbial; microorganism; molecular dynamics; mutant; novel; polar environment; protein folding; protein misfolding; protein structure; simulation

Project Summary Understanding how proteins fold is a central quest in biology. Studied for over 50 years, investigations of soluble protein folding have proven invaluable for dissecting the molecular basis of a multitude of diseases. By comparison, folding studies of membrane proteins (MPs) lag far behind. The knowledge gained from soluble protein studies cannot simply be transferred to inferences about MPs because their solvents are different. The balance of forces encoding a MP embedded in a lipid bilayer must be distinct from that of soluble proteins in water. Our research efforts contribute to filling this key gap in the understanding the physical chemistry of membrane proteins. We will experimentally determine of energetic forces stabilizing membrane proteins along the steeply changing polarity gradient of the phospholipid bilayer interface. These efforts will be complemented by molecular simulations and mathematic systems modeling. In addition, we aim to incorporate novel techniques to our toolbox to address the energetic importance of backbone hydrogen bonds in transmembrane proteins. Our results have broad ranging impact in the field at large through contributions to information databases used in training computational algorithms and by their incorporation in physically realistic mechanisms for protein folding catalysis by cellular machines.

项目摘要 了解蛋白质如何折叠是生物学的核心任务。学习超过50年 多年来，可溶性蛋白质折叠的研究已被证明是非常宝贵的解剖， 许多疾病的分子基础。相比之下，膜的折叠研究 蛋白质（MP）远远落后。从可溶性蛋白质研究中获得的知识 不能简单地转移到关于MP的推论，因为它们的溶剂是 不同.编码包埋在脂质双层中的MP的力的平衡必须是 与水溶性蛋白质不同。 我们的研究工作有助于填补这一关键空白， 膜蛋白的物理化学我们将通过实验确定 迫使稳定膜蛋白沿着急剧变化的极性梯度， 磷脂双层界面。这些努力将得到分子 仿真和数学系统建模。此外，我们的目标是将新的 我们的工具箱，以解决能源的重要性骨干氢技术 跨膜蛋白中的键。 我们的研究结果通过对以下方面的贡献，在整个领域产生了广泛的影响： 用于训练计算算法的信息数据库， 在蛋白质折叠催化的物理现实机制中， 机械.

项目成果

E. coli outer membrane and interactions with OmpLA.

• DOI: 10.1016/j.bpj.2014.04.024
• 发表时间: 2014-06
• 期刊: Biophysical journal
• 影响因子: 3.4
• 作者: E. Wu;P. Fleming;M. S. Yeom;G. Widmalm;Jeffery B. Klauda;K. Fleming;W. Im

Revisiting macromolecular hydration with HullRadSAS.

使用 HullRadSAS 重新审视大分子水合。

• DOI: 10.1007/s00249-022-01627-8
• 发表时间: 2023
• 期刊: European biophysics journal : EBJ
• 作者: Fleming,PatrickJ;Correia,JohnJ;Fleming,KarenG
• 通讯作者: Fleming,KarenG

Taking deterministic control of membrane protein monomer-dimer measurements.

对膜蛋白单体-二聚体测量进行确定性控制。

• DOI: 10.1085/jgp.201711913
• 发表时间: 2018
• 期刊: The Journal of general physiology
• 作者: Fleming,KarenG