Static and dynamic properties of antibody proteins in solution - the effects of crowding and charge-tuning

溶液中抗体蛋白的静态和动态特性 - 拥挤和电荷调节的影响

• 批准号: 316738961
• 负责人: Professor Dr. Frank Schreiber
• 金额: --
• 依托单位: Institut für Angewandte Physik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/316738961?language=en
• 关键词: Static; dynamic; properties; antibody; proteins

The efficient medical dosage of antibodies requires high concentrations in aqueous solutions. These solutions can in addition contain other molecules, denoted crowding agents, which help to increase the maximum protein concentration or circumvent protein aggregation. We propose to study both static and dynamic properties of highly concentrated aqueous antibody solutions using small-angle scattering, neutron spectroscopy, and complementary techniques. In particular, we address the effects of macromolecular crowding and ion-induced charges on the effective protein-protein interactions, phase behavior, and global as well as internal dynamics of antibodies in solution. We also focus on the dynamic, transient, or static cluster phases in this system depending on the employed physical parameters. The systematic investigation will cover both the effect of self-crowding by the antibody proteins themselves as well as by external crowding agents such as other proteins (e.g. BSA), polymers (e.g. PEG), and sugars (e.g. trehalose). With view at the peculiar three-lobed conformation of immunoglobulin antibody proteins, the project will in particular be guided by the role and importance of the protein shape in the determination of the static and dynamic properties of the protein solutions. Whilst addressing questions related to biophysics and biomedicine, we will employ both experimental and theoretical concepts and methods from soft-matter physics. These methods provide a unique access to molecular length scales and to picosecond to nanosecond time scales of molecular motions. Our proposed study addresses important questions regarding applied protein science as well as fundamental mechanisms of crowding in solutions of anisotropic particles.

抗体的有效医疗剂量需要水溶液中的高浓度。这些溶液还可以包含其他分子，表示拥挤的药物，这有助于增加最大蛋白质浓度或规避蛋白质聚集。我们建议使用小角度散射，中子光谱和互补技术研究高度浓缩水溶液溶液的静态和动态特性。特别是，我们解决了大分子拥挤和离子诱导的电荷对溶液中抗体的有效蛋白质 - 蛋白质相互作用，相位行为以及全局动力学的影响。我们还专注于该系统中的动态，瞬态或静态群集阶段，具体取决于使用的物理参数。该系统研究将涵盖抗体蛋白本身的自我拥挤的影响，以及外部拥挤剂，例如其他蛋白质（例如BSA），聚合物（例如PEG）和糖（例如Trehalose）的影响。从免疫球蛋白抗体蛋白的特殊三叶构象看来，该项目尤其受蛋白质形状在确定蛋白质溶液的静态和动态特性中的作用和重要性的指导。在解决与生物物理学和生物医学有关的问题的同时，我们将采用实验和理论概念以及软性物理学的方法。这些方法为分子长度尺度提供了独特的访问权限，并访问了分子运动的纳秒时间尺度。我们提出的研究解决了有关应用蛋白科学的重要问题以及各向异性颗粒溶液中拥挤的基本机制。

项目成果

Two time scales for self and collective diffusion near the critical point in a simple patchy model for proteins with floating bonds.

具有浮动键的蛋白质的简单斑块模型中接近临界点的自我扩散和集体扩散的两个时间尺度

• DOI: 10.1039/c8sm00599k
• 发表时间: 2018
• 期刊: Soft matter
• 影响因子: 3.4
• 作者: J. Bleibel;M. Habiger;M. Lütje;F. Hirschmann;F. Roosen-Runge;T. Seydel;F. Zhang;F. Schreiber;M. Oettel
• 通讯作者: M. Oettel

Following Protein Dynamics in Real Time during Crystallization

• DOI: 10.1021/acs.cgd.9b00858
• 发表时间: 2019-10
• 期刊: Crystal Growth & Design
• 影响因子: 3.8
• 作者: C. Beck;M. Grimaldo;F. Roosen‐Runge;R. Maier;O. Matsarskaia;Michal K. Braun;Benedikt Sohmen;O. Czakkel;R. Schweins;Fajun Zhang;T. Seydel;F. Schreiber

Dynamics of proteins in solution

• DOI: 10.1017/s0033583519000027
• 发表时间: 2019-01-01
• 期刊: QUARTERLY REVIEWS OF BIOPHYSICS
• 影响因子: 6.1
• 作者: Grimaldo, Marco;Roosen-Runge, Felix;Seydel, Tilo
• 通讯作者: Seydel, Tilo