Computational Studies of Biomolecular Structure and Function

生物分子结构和功能的计算研究

基本信息

  • 批准号:
    418679-2013
  • 负责人:
  • 金额:
    $ 3.21万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2019
  • 资助国家:
    加拿大
  • 起止时间:
    2019-01-01 至 2020-12-31
  • 项目状态:
    已结题

项目摘要

Many important biological processes, such as signalling, recognition, and transport, as well as infection and immune response, involve interactions between peptides or proteins and lipid. The detailed characterization of these processes is currently impeded by the difficulty in elucidating the structure of peptides and proteins in the anisotropic and chemically complex environment provided by lipid bilayers. For these reasons, structural studies of membrane proteins often employ detergent molecules, which mimic the chemical properties of lipid bilayers, to solubilize the proteins, making them more amenable to crystallization. However, at present there are no general methods for the experimental determination of membrane protein structure, underscoring the need for reliable predictive algorithms. A powerful approach to gain insight into the structure and function of biomolecules is to use computer simulations, but the scope of these studies is currently limited by the long time scales required to investigate the folding and self-assembly of proteins and peptides in lipid.In this proposal, we will address these limitations by combining novel sampling algorithms developed in our laboratory with massive computational resources awarded to us by Compute Canada. These extraordinary resources put us in a unique position to examine the interaction of peptides and proteins with lipid and detergent molecules in four different but complementary studies. In two of these projects, we will study how lipid and detergent self-assemblies solvate proteins and determine their fold. Reciprocally, in the other two studies, we will examine how the self-assembly of peptides affects the structure of lipid bilayers.This work will provide advanced computational tools for the much-needed prediction of membrane protein structure, and will help improve detergent-based approaches to elucidate the structure of membrane proteins experimentally. Just as important, the proposed studies will afford fundamental insight into the molecular basis for the action of antimicrobial peptides and the toxicity of peptides derived from prions implicated in "mad cow" and chronic wasting diseases, two serious threats to Canadian wildlife and agriculture.
许多重要的生物学过程,如信号传导、识别和转运,以及感染和免疫反应,都涉及多肽或蛋白质与脂质之间的相互作用。由于在脂质双分子层提供的各向异性和化学复杂环境中难以阐明肽和蛋白质的结构,这些过程的详细表征目前受到阻碍。由于这些原因,膜蛋白的结构研究经常使用清洁剂分子,它模仿脂质双分子层的化学性质,来溶解蛋白质,使它们更容易结晶。然而,目前尚无通用的膜蛋白结构实验测定方法,因此需要可靠的预测算法。利用计算机模拟是了解生物分子结构和功能的一种有效方法,但目前这些研究的范围受到研究脂质中蛋白质和肽的折叠和自组装所需的长时间尺度的限制。在本提案中,我们将通过将我们实验室开发的新颖采样算法与加拿大计算机公司授予我们的大量计算资源相结合来解决这些限制。这些非凡的资源使我们处于一个独特的位置,以检查肽和蛋白质与脂质和洗涤剂分子的相互作用,在四个不同的,但互补的研究。在其中两个项目中,我们将研究脂质和洗涤剂如何自组装溶剂化蛋白质并确定它们的折叠。反过来,在其他两个研究中,我们将研究肽的自组装如何影响脂质双分子层的结构。这项工作将为急需的膜蛋白结构预测提供先进的计算工具,并将有助于改进基于洗涤剂的方法来实验阐明膜蛋白的结构。同样重要的是,拟议的研究将对抗菌肽作用的分子基础以及与“疯牛病”和慢性消耗性疾病有关的朊病毒衍生的肽的毒性提供根本性的见解,这两种疾病对加拿大野生动物和农业构成严重威胁。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Pomès, Régis其他文献

Pomès, Régis的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Pomès, Régis', 18)}}的其他基金

Computational Studies of Biomolecular Structure and Function
生物分子结构和功能的计算研究
  • 批准号:
    418679-2013
  • 财政年份:
    2016
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Discovery Grants Program - Individual
Rational design of non-immunogenic elastin-based materials for applications in drug delivery
用于药物输送应用的非免疫原性弹性蛋白材料的合理设计
  • 批准号:
    492839-2015
  • 财政年份:
    2016
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Engage Grants Program
Computational Studies of Biomolecular Structure and Function
生物分子结构和功能的计算研究
  • 批准号:
    418679-2013
  • 财政年份:
    2015
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Studies of Biomolecular Structure and Function
生物分子结构和功能的计算研究
  • 批准号:
    418679-2013
  • 财政年份:
    2014
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Studies of Biomolecular Structure and Function
生物分子结构和功能的计算研究
  • 批准号:
    418679-2013
  • 财政年份:
    2013
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Discovery Grants Program - Individual

相似海外基金

CAREER: Experimental and Computational Studies of Biomolecular Topology
职业:生物分子拓扑的实验和计算研究
  • 批准号:
    2336744
  • 财政年份:
    2024
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Continuing Grant
CAREER: Nonlinear Infrared Studies of Biomolecular Coacervation
职业:生物分子凝聚的非线性红外研究
  • 批准号:
    2239472
  • 财政年份:
    2023
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Continuing Grant
Biomolecular NMR studies of protein binding and allostery
蛋白质结合和变构的生物分子核磁共振研究
  • 批准号:
    552481-2020
  • 财政年份:
    2020
  • 资助金额:
    $ 3.21万
  • 项目类别:
    University Undergraduate Student Research Awards
In-situ studies of biomolecular assisted Li-air batteries and studies of biobased redox mediators and ORR catalysts
生物分子辅助锂空气电池的原位研究以及生物基氧化还原介质和ORR催化剂的研究
  • 批准号:
    2279750
  • 财政年份:
    2019
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Studentship
A biomolecular purification system for biophysical studies of protein synthesis
用于蛋白质合成生物物理研究的生物分子纯化系统
  • 批准号:
    10387206
  • 财政年份:
    2019
  • 资助金额:
    $ 3.21万
  • 项目类别:
Experimental Studies of the Structures, Energetics, and Reactions of Gas Phase Self-Assembled Biomolecular Ionic Complexes
气相自组装生物分子离子配合物的结构、能量学和反应的实验研究
  • 批准号:
    RGPIN-2014-04429
  • 财政年份:
    2018
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Discovery Grants Program - Individual
Spin Labeling Studies of Biomolecular Flexibility and Hydration
生物分子柔韧性和水合的自旋标记研究
  • 批准号:
    1715384
  • 财政年份:
    2017
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Standard Grant
Experimental Studies of the Structures, Energetics, and Reactions of Gas Phase Self-Assembled Biomolecular Ionic Complexes
气相自组装生物分子离子配合物的结构、能量学和反应的实验研究
  • 批准号:
    RGPIN-2014-04429
  • 财政年份:
    2017
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Discovery Grants Program - Individual
Quantitative, Mechanistic Studies of Biomolecular Recognition
生物分子识别的定量、机制研究
  • 批准号:
    10404672
  • 财政年份:
    2016
  • 资助金额:
    $ 3.21万
  • 项目类别:
Computational Studies of Biomolecular Structure and Function
生物分子结构和功能的计算研究
  • 批准号:
    418679-2013
  • 财政年份:
    2016
  • 资助金额:
    $ 3.21万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了