Phase boundaries and liquid structure of concentrated eye lens protein mixtures

浓缩眼晶状体蛋白质混合物的相界和液体结构

• 批准号: 8574560
• 负责人: George Thurston
• 金额: $ 36.13万
• 依托单位: ROCHESTER INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8574560
• 关键词: Affect; Amino Acids; Biology; Blindness; Buffers; Cataract; Cattle; Cells; Charge; Chemicals; Chemistry; Computer Simulation; Coupling; Crystalline Lens; Crystallins; Data; Data Analyses; Dependence; Disease; Electrostatics; Equilibrium; Eye Lens Protein; Free Energy; Funding; Goals; Health; Human; Investigation; Ionic Strengths; Joints; Knowledge; Life; Liquid substance; Mathematics; Measurement; Measures; Modeling; Molecular; Molecular Weight; Neutrons; Nuclear Magnetic Resonance; Phase; Physics; Prevention; Proteins; Research; Research Personnel; Roentgen Rays; Solutions; Structure; System; Temperature; Testing; Thermodynamics; Titrations; Training; Ursidae Family; alpha-Crystallins; aqueous; base; beta-Crystallins; computer science; density; gamma S crystallin; gamma-Crystallins; lens protein; light scattering; protonation; public health relevance; response; sound

Cataract disease, the leading cause of blindness worldwide, is the end result of increased scattering of light within the human ocular lens. The proposed research continues to establish the multi-component phase diagram of concentrated, aqueous eye lens crystallin protein mixtures, together with its statistical-thermodynamic molecular basis. Neutron scattering, X-ray scattering, nuclear magnetic resonance, light scattering, statistical thermodynamic modeling, and computer simulation will be used to (1) test the prediction of non-monotonic dependence of alpha-gamma stability on interaction strength, and refine knowledge of the underlying molecular origins of the alpha-gamma phase diagram by testing ternary free energy models on available scattering data, (2) perform detailed experimental and theoretical investigation of orientation- dependent interactions between gamma crystallins, while focusing in part on screened, charge-regulated electrostatic interactions, and (3) systematically measure and analyze the phase diagrams and light scattering of controlled, quaternary aqueous mixtures of lens proteins, including the key alpha, beta, gamma, and buffer system. Each of these steps will involve the training of undergraduate researchers, who can be drawn from physics, chemistry, biology, mathematics, and computer science, and each step is an essential part of providing a sound molecular understanding of the light scattering, phase diagram, and dynamics of concentrated solutions and mixtures of gamma, alpha, and beta crystallin, and as such bears on the molecular origins of cataract.

白内障是全世界致盲的主要原因，这是最终的结果。 人类晶状体内的光散射增加。建议数 研究继续建立多组分相图 浓缩的含水眼晶状体晶体蛋白混合物及其 统计热力学分子基础。中子散射、X射线散射、 核磁共振，光散射，统计热力学模型， 并用计算机模拟的方法(1)检验非单调的预测 α-伽马稳定性对相互作用强度的依赖，并进行了细化 关于α-伽马相潜在分子起源的知识 根据现有散射数据测试三元自由能模型的示意图，(2) 对定向进行详细的实验和理论研究- 伽马晶体蛋白之间的依赖相互作用，同时部分集中在 屏蔽的、电荷调节的静电相互作用，以及(3)系统地 测量并分析了受控样品的相图和光散射， 晶状体蛋白质的四元水溶液混合物，包括关键的α，β， 伽马和缓冲系统。这些步骤中的每一步都将涉及培训 本科生研究人员，他们可以从物理，化学，生物， 数学和计算机科学，每一步都是 提供对光散射、位相的合理的分子理解 图，以及浓缩液和伽马，α， 和β晶体蛋白，因此与白内障的分子起源有关。

项目成果

Mathematical and computational aspects of quaternary liquid mixing free energy measurement using light scattering.

使用光散射测量四元液体混合自由能的数学和计算方面。

• DOI: 10.1063/1.4736837
• 发表时间: 2012
• 期刊: The Journal of chemical physics
• 作者: Wahle,ChrisW;Ross,DavidS;Thurston,GeorgeM
• 通讯作者: Thurston,GeorgeM

On inferring liquid-liquid phase boundaries and tie lines from ternary mixture light scattering.

从三元混合物光散射推断液-液相边界和联络线。

• DOI: 10.1063/1.4731710
• 发表时间: 2012
• 期刊: The Journal of chemical physics
• 作者: Wahle,ChrisW;Ross,DavidS;Thurston,GeorgeM
• 通讯作者: Thurston,GeorgeM

Model for evaluating patterned charge-regulation contributions to electrostatic interactions between low-dielectric spheres.

用于评估图案化电荷调节对低介电球之间静电相互作用的贡献的模型。

• DOI: 10.1103/physreve.82.031402
• 发表时间: 2010
• 期刊: Physical review. E, Statistical, nonlinear, and soft matter physics
• 作者: Hollenbeck,Dawn;Martini,KMichael;Langner,Andreas;Harkin,Anthony;Ross,DavidS;Thurston,GeorgeM
• 通讯作者: Thurston,GeorgeM

Charge-regulation phase transition on surface lattices of titratable sites adjacent to electrolyte solutions: An analog of the Ising antiferromagnet in a magnetic field.

邻近电解质溶液的可滴定位点表面晶格上的电荷调节相变：磁场中伊辛反铁磁体的类似物。

• DOI: 10.1103/physreve.92.062123
• 发表时间: 2015
• 期刊: Physical review. E, Statistical, nonlinear, and soft matter physics
• 作者: Shore,JoelD;Thurston,GeorgeM
• 通讯作者: Thurston,GeorgeM

Statistical-thermodynamic model for light scattering from eye lens protein mixtures.

眼晶状体蛋白质混合物光散射的统计热力学模型。

• DOI: 10.1063/1.4974155
• 发表时间: 2017
• 期刊: The Journal of chemical physics
• 作者: Bell,MichaelM;Ross,DavidS;Bautista,MaurinoP;Shahmohamad,Hossein;Langner,Andreas;Hamilton,JohnF;Lahnovych,CarrieN;Thurston,GeorgeM
• 通讯作者: Thurston,GeorgeM