Ion-Ion Interactions and the Reverse Hofmeister Effect

离子-离子相互作用和逆霍夫迈斯特效应

基本信息

  • 批准号:
    10202645
  • 负责人:
  • 金额:
    $ 37.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-08-01 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary Although the properties of dissolved organic solutes and salts have been studied for over 130 years, we know little of the laws governing how they interact. Consider for example the fact that NaI can lead to an increase in the solubility of a protein (the Hofmeister Effect) or bring about a decrease in solubility and lead to precipitation of a protein (the Reverse Hofmeister Effect, RHE). This application concerns the latter. Our understanding of the molecular interactions behind the RHE is limited. Indeed, it is only in the last decade that it has been confirmed that the key non-covalent interactions are those between the anion of the salt and positively charged groups on the solute. Beyond this, details are sparse: We know little about the magnitude of such interactions and whether they are dominated by Coulombic or dispersion interactions; we know little about the existence of specific ion-pairs that might dominate the precipitation of a solute; and we know little about the mechanisms of the aggregation and precipitation pathway(s). To develop an understanding of these we outline: 1) studies with model hosts designed to probe ion-ion pairing structurally and thermodynamically, and hence reveal details of how these lead to aggregation and precipitation; 2) molecular dynamics (MD) simulations designed to reveal atomistic details of these ion pairs, and the role water plays in modulating their thermodynamics of interaction, and; 3) studies with proteins that, building on our understanding of model hosts and MD simulations, will begin to systematically qualify and quantify how the RHE is manifest in proteins, and the specific ion-ion interactions behind this phenomenon. These studies will address the following scientific questions: · What are the specific ion-ion interactions pertinent to the RHE? · What are the specific structural features and thermodynamics of these ion-ion interactions? · Are there qualitative and quantitative links between the nature of ion pairing and the aggregation and precipitation of small molecules? · Do anion-protein interactions influence the structure, stability, and aggregation of proteins in specific, determinable ways? · Can the RHE in proteins be used as a signature to characterize/identify proteins? · Can the RHE in proteins be attributed to specific anion-protein interactions? Answering these questions will improve our understanding of the solubility of small molecules common to the pharmaceutical industry, and lead to a clearer picture of the often bewildering and contradictory RHE in proteins. This latter point is not only key to determining new ways to purify and crystallize proteins, but is also crucial to understanding the irreversible deposition of proteins in prion diseases and thrombosis.
项目摘要 虽然溶解有机溶质和盐的性质已经研究了130多年, 对它们如何相互作用的规律知之甚少。例如,考虑NaI可以导致 增加蛋白质的溶解度(霍夫迈斯特效应)或降低溶解度并导致 反向霍夫迈斯特效应(Reverse Hofmeister Effect,RHE)本申请涉及后者。 我们对RHE背后的分子相互作用的理解是有限的。其实,只有在最后。 近十年来,已经证实关键的非共价相互作用是阴离子与阴离子之间的相互作用。 盐和溶质上带正电荷的基团。除此之外,细节很少:我们对 这种相互作用的大小,以及它们是否由库仑或色散相互作用主导;我们 我们对可能支配溶质沉淀的特定离子对的存在知之甚少; 对聚集和沉淀途径的机制知之甚少。开发一个 我们概述了对这些的理解:1)设计用于探测离子-离子配对结构的模型宿主的研究 并因此揭示了这些如何导致聚集和沉淀的细节; 2) 分子动力学(MD)模拟旨在揭示这些离子对的原子细节,以及水的作用 在调节它们相互作用的热力学中起作用; 3)对蛋白质的研究, 了解模型主机和MD模拟,将开始系统地定性和量化如何 RHE表现在蛋白质中,以及这种现象背后的特定离子-离子相互作用。 这些研究将解决以下科学问题: ·与RHE相关的特定离子-离子相互作用是什么? ·这些离子-离子相互作用的具体结构特征和热力学是什么? ·离子配对的性质与聚集之间是否存在定性和定量联系, 小分子的沉淀? ·阴离子-蛋白质相互作用是否影响蛋白质的结构、稳定性和聚集, 确定的方式? ·蛋白质中的RHE是否可以用作表征/识别蛋白质的特征? ·蛋白质中的RHE能归因于特定的阴离子-蛋白质相互作用吗? 回答这些问题将有助于我们更好地理解常见的小分子的溶解性。 到制药行业,并导致一个更清晰的画面往往令人困惑和矛盾的RHE在 proteins.后一点不仅是确定纯化和结晶蛋白质的新方法的关键, 对于了解朊病毒疾病和血栓形成中蛋白质的不可逆沉积至关重要。

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Buffer and Salt Effects in Aqueous Host-Guest Systems: Screening, Competitive Binding, or Both?
水溶液中的缓冲液和盐效应:筛查,竞争性结合,还是两者兼而有之?
Dynamic Light Scattering - an all-purpose guide for the supramolecular chemist.
动态光散射 - 超分子化学家的通用指南。
  • DOI:
    10.1080/10610278.2019.1629438
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Wishard,Anthony;Gibb,BruceC
  • 通讯作者:
    Gibb,BruceC
Anion binding to ubiquitin and its relevance to the Hofmeister effects.
阴离子与泛素结合及其与Hofmeister效应的相关性。
  • DOI:
    10.1039/d0sc04245e
  • 发表时间:
    2020-11-04
  • 期刊:
  • 影响因子:
    8.4
  • 作者:
    Yao W;Wang K;Wu A;Reed WF;Gibb BC
  • 通讯作者:
    Gibb BC
Bright G-Quadruplex Nanostructures Functionalized with Porphyrin Lanterns.
  • DOI:
    10.1021/jacs.9b03250
  • 发表时间:
    2019-08-14
  • 期刊:
  • 影响因子:
    15
  • 作者:
    Pathak P;Yao W;Hook KD;Vik R;Winnerdy FR;Brown JQ;Gibb BC;Pursell ZF;Phan AT;Jayawickramarajah J
  • 通讯作者:
    Jayawickramarajah J
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BRUCE C GIBB其他文献

BRUCE C GIBB的其他文献

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{{ truncateString('BRUCE C GIBB', 18)}}的其他基金

Using deep-cavity cavitands to study supramolecular chemistry in water
利用深腔空配体研究水中的超分子化学
  • 批准号:
    8477215
  • 财政年份:
    2012
  • 资助金额:
    $ 37.24万
  • 项目类别:
Using deep-cavity cavitands to study supramolecular chemistry in water
利用深腔空配体研究水中的超分子化学
  • 批准号:
    8258409
  • 财政年份:
    2012
  • 资助金额:
    $ 37.24万
  • 项目类别:
Using deep-cavity cavitands to study supramolecular chemistry in water
利用深腔空配体研究水中的超分子化学
  • 批准号:
    8627614
  • 财政年份:
    2012
  • 资助金额:
    $ 37.24万
  • 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
  • 批准号:
    7171524
  • 财政年份:
    2006
  • 资助金额:
    $ 37.24万
  • 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
  • 批准号:
    7575601
  • 财政年份:
    2006
  • 资助金额:
    $ 37.24万
  • 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
  • 批准号:
    7760945
  • 财政年份:
    2006
  • 资助金额:
    $ 37.24万
  • 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
  • 批准号:
    7032211
  • 财政年份:
    2006
  • 资助金额:
    $ 37.24万
  • 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
  • 批准号:
    7343269
  • 财政年份:
    2006
  • 资助金额:
    $ 37.24万
  • 项目类别:

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