Studies of molecular crowding

分子拥挤的研究

• 批准号: 9148734
• 负责人: Allen P Minton
• 金额: $ 18万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9148734
• 关键词: Accounting; Adsorption; Age; Appearance; Behavior; Biological; Complex; Crowding; Data; Dependence; Disaccharides; Disease; Elements; Free Energy; Goals; Individual; Lactalbumin; Liquid substance; Measures; Methods; Modeling; Mole the mammal; Molecular; Monosaccharides; Monte Carlo Method; Muramidase; Neurodegenerative Disorders; Oligosaccharides; Proteins; Solutions; Surface; System; Temperature; Thermodynamics; Time; Tracer; Trisaccharides; Work; base; equilibrium model; macromolecule; sugar; theories

1. A model for the effect of time-dependent macromolecular crowding upon the rate of protein fibrillation was developed and presented as a possible explanation for the similar age dependence of the appearance of diverse neurodegenerative diseases that are attributed to the aggregation or fibrillation of different proteins with very different intrinsic colloidal stabilities (A. Minton). 2. An equilibrium model for the combined effect of macromolecular crowding and surface adsorption upon protein fibrillation was developed. The model predicts a highly cooperative transition between a slightly self-associating tracer species in bulk solution and a highly self-associated adsorbed tracer. Model estimates of the tendency of linear oligomers of various sizes to adsorb in the presence of unreactive crowders occupying various fractions of total solution volume are compared with the results of Monte Carlo simulations (T. Hoppe, A. Minton) 3. The effect of several monosaccharides and oligosaccharides on the thermal stability of two proteins (alpha-lactalbumin and lysozyme) at pH 7 has been measured via the temperature dependence of absorbance and ellipticity. The effect per mole of three monosaccharides on the free energy of unfolding is indistinguishable, that of two disaccharides approximately twice as large, that of a trisaccharide approximately three times as large and that of a tetrasaccharide approximately four times as much. The data were accounted for quantitatively by a simple statistical-thermodynamic model in which the interaction between all sugars and both proteins is assumed to be essentially entirely due to steric repulsion. (F. Ahmad, I. Beg, A. Minton)

1. 开发了一种时间依赖性大分子拥挤对蛋白质纤维颤动率影响的模型，并提出了一种可能的解释，即由于不同蛋白质的聚集或纤维颤动而导致的多种神经退行性疾病的出现具有相似的年龄依赖性具有非常不同的内在胶体稳定性（A. Minton）。 2.建立了大分子拥挤和表面吸附对蛋白质原纤化的综合作用的平衡模型。 该模型预测了本体溶液中的轻微自缔合示踪剂物种与高度自缔合吸附示踪剂之间的高度合作转变。 将模型估计的各种尺寸的线性低聚物在占据总溶液体积的不同部分的非反应性拥挤剂存在下吸附的趋势与蒙特卡罗模拟的结果进行比较（T. Hoppe，A. Minton） 3. 在 pH 7 下，几种单糖和寡糖对两种蛋白质（α-乳清蛋白和溶菌酶）热稳定性的影响已通过吸光度和椭圆率的温度依赖性进行了测量。 每摩尔三种单糖对解折叠自由能的影响是无法区分的，两种二糖的影响大约是两倍，三糖的影响大约是三倍，四糖的影响大约是四倍。 这些数据通过一个简单的统计热力学模型进行定量解释，其中假设所有糖和两种蛋白质之间的相互作用基本上完全是由于空间排斥造成的。 （F. 艾哈迈德、I. 贝格、A. 明顿）

项目成果

Modulation of functionally significant conformational equilibria in adenylate kinase by high concentrations of trimethylamine oxide attributed to volume exclusion.

高浓度三甲胺氧化物对腺苷酸激酶中具有功能意义的构象平衡的调节归因于体积排斥。

• 发表时间: 2011-06-22
• 影响因子: 3.4
• 作者: Nagarajan, Sureshbabu;Amir, Dan;Grupi, Asaf;Goldenberg, David P;Minton, Allen P;Haas, Elisha
• 通讯作者: Haas, Elisha

Attractive protein-polymer interactions markedly alter the effect of macromolecular crowding on protein association equilibria.

有吸引力的蛋白质-聚合物相互作用显着改变大分子拥挤对蛋白质缔合平衡的影响。

• 发表时间: 2010-08-04
• 影响因子: 3.4
• 作者: Jiao, Ming;Li, Hong;Chen, Jie;Minton, Allen P;Liang, Yi
• 通讯作者: Liang, Yi