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追求。研究了50多个 多年来，对可溶性蛋白折叠的研究已证明是无价的。 多种疾病的分子基础。相比之下，膜的折叠研究 蛋白质（MPS）滞后。从可溶性蛋白研究中获得的知识 不能简单地转移到有关国会议员的推论，因为它们的溶剂是 不同的。编码嵌入脂质双层的MP的力平衡必须是 与水中的可溶性蛋白不同。 我们的研究工作有助于填补这一关键差距 膜蛋白的物理化学。我们将通过实验确定能量 力沿着陡峭变化的极性梯度稳定膜蛋白 磷脂双层界面。这些努力将由分子补充 仿真和数学系统建模。此外，我们的目标是纳入小说 我们工具箱的技术来解决骨干氢的能量重要性 跨膜蛋白中的键。 我们的结果通过贡献了 培训计算算法中使用的信息数据库及其 融合到物理逼真的机制中，用于蛋白质折叠催化细胞的催化 机器。

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