Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement

计算纳米生物物理学:约束中生物分子的建模和模拟

基本信息

  • 批准号:
    RGPIN-2014-06091
  • 负责人:
  • 金额:
    $ 1.38万
  • 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:
    2015
  • 资助国家:
    加拿大
  • 起止时间:
    2015-01-01 至 2016-12-31
  • 项目状态:
    已结题

项目摘要

Current fabrication technology makes it possible to design and build devices on the nanometer scale. In fact, nanofluidic devices enable the containment of single molecules such as proteins and DNA, which are only several nanometers wide. This ability has ushered in a new era of single molecule studies. Moreover, the tight confinement of the molecules in these devices can be used to influence their configuration. For example, a DNA strand in a 10 nm wide nanotube remains extended, unlike its ball-like configuration in bulk fluid. Nanofluidic devices are thus ideal for the isolation of single biomolecules allowing them to be identified, characterized, manipulated, and even modified. Given the importance of DNA and proteins in biomedical research, nanofluidic devices promise to be central in the development of next generation medical devices, diagnostics, and therapies. In order to capitalize on these capabilities and develop applications, it is necessary to know in detail how biomolecules behave within these devices. The small length scale of the systems and short time scale of the dynamics present significant challenges for precise experimental measurements. Hence, computer simulations are an invaluable tool in probing the physics of biomolecules at the nanoscale as they can simulate the behaviour of biomolecules in nanofluidic devices at extremely high spatial and temporal resolutions even for complex systems. Our research program uses computer simulations to study biomolecules in confinement, with a focus on three particular systems. The first system is the passage of polymers such as DNA across membranes (known as translocation) through small, constricting pores (called nanopores). This process is ubiquitous in nature as it is arises whenever DNA, RNA, or proteins cross cell membranes. It is also central to a number of emerging nanotechnolgies, the most prominent of which is the use of nanopores for rapid, inexpensive sequencing of even single strands of DNA. This technology, which is the focus of the National Human Genome Research Institute's $17M DNA sequencing project, is set to revolutionize health care by greatly facilitating personalized medicine. Our second system of study is the nanopit system. In this setup, DNA is confined in a slit between two walls, where one wall is periodically etched with pits. Since DNA prefers to occupy regions of less confinement, it tends to fill the pits. Shorter polymers, which can fit into one pit, become stuck while longer polymers continue to move through the system by hopping between pits. Applications of these dynamics include sorting DNA by length and manipulating DNA into prescribed configurations (e.g., stretched between two pits). The third system is known as CLIC (Convex Lens Induced Confinement) in which a solution of DNA strands is placed between two coverslips and a convex lens is lowered onto the top coverslip, pressing down and forming a convex upper boundary. This unique setup allows for a wide range of confinements to be observed simultaneously and thus is an ideal platform for studying the fundamental properties of DNA. In each project, we will collaborate with experimental research groups. Through our collaborations, unique to each project, our detailed results will give insight into the experimental data which will in turn help refine the simulation approaches. Through this fundamental knowledge, we will propose and explore applications using nanofludics to identify, characterize, and manipulate biomolecules – such as sequencing DNA using nanopores. This technology will be part of the transformation of medical diagnostic, monitoring, and therapeutic approaches that are tailored to individual needs based on genetic make-up.
目前的制造技术使在纳米尺度上设计和制造器件成为可能。事实上,纳米流体设备能够遏制蛋白质和DNA等只有几纳米宽的单分子。这种能力开启了单分子研究的新纪元。此外,这些器件中分子的严格限制可以用来影响它们的配置。例如,10纳米宽的纳米管中的DNA链保持伸展,不同于其在大块流体中的球状构型。因此,纳米流体设备是分离单个生物分子的理想选择,可以对其进行识别、表征、操作甚至修饰。鉴于DNA和蛋白质在生物医学研究中的重要性,纳米流体设备有望在下一代医疗设备、诊断和治疗的开发中发挥核心作用。 为了充分利用这些能力并开发应用,有必要详细了解生物分子在这些设备中的行为。系统的小长度尺度和动力学的短时间尺度对精确的实验测量提出了巨大的挑战。因此,计算机模拟是在纳米尺度上探索生物分子物理的宝贵工具,因为它们可以在极高的空间和时间分辨率下模拟生物分子在纳米流体设备中的行为,即使对于复杂的系统也是如此。 我们的研究项目使用计算机模拟来研究受限条件下的生物分子,重点是三个特定的系统。第一个系统是DNA等聚合物穿过细胞膜(称为移位)通过狭窄的小孔(称为纳米孔)。这个过程在自然界中是普遍存在的,因为每当DNA、RNA或蛋白质穿过细胞膜时就会发生这种过程。它也是许多新兴纳米技术的核心,其中最突出的是使用纳米孔对DNA单链进行快速、廉价的测序。这项技术是美国国家人类基因组研究所耗资1700万美元的DNA测序项目的重点,它将极大地促进个性化医疗,从而为医疗保健带来革命性的变化。我们的第二个研究系统是纳米IT系统。在这种装置中,DNA被限制在两面墙之间的狭缝中,其中一面墙上周期性地蚀刻有凹坑。由于DNA倾向于占据较少受限制的区域,它往往会填满凹坑。较短的聚合物可以放入一个凹坑中,当较长的聚合物通过在凹坑之间跳跃继续在系统中移动时,会被卡住。这些动力学的应用包括按长度对DNA进行分类和将DNA处理成规定的构型(例如,在两个凹坑之间拉伸)。第三个系统被称为CLIC(凸透镜诱导约束),在该系统中,将DNA链的溶液放置在两个盖片之间,并将凸透镜降到顶盖片上,向下压下并形成凸上边界。这种独特的设置允许同时观察大范围的限制,因此是研究DNA基本性质的理想平台。 在每个项目中,我们都将与实验研究小组合作。通过我们的合作,每个项目都是独一无二的,我们的详细结果将使我们深入了解实验数据,这反过来将有助于改进模拟方法。通过这些基础知识,我们将提出并探索使用纳米流体来识别、表征和操纵生物分子的应用--例如使用纳米孔对DNA进行测序。这项技术将是医疗诊断、监测和治疗方法转变的一部分,这些方法是基于基因构成根据个人需求量身定做的。

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 }}

deHaan, Hendrick其他文献

deHaan, Hendrick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('deHaan, Hendrick', 18)}}的其他基金

Combining Deep Learning and Coarse Grained Simulation Methods to Study High-Dimensional NanoBiophysical Systems
结合深度学习和粗粒度模拟方法来研究高维纳米生物物理系统
  • 批准号:
    RGPIN-2020-07145
  • 财政年份:
    2022
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Combining Deep Learning and Coarse Grained Simulation Methods to Study High-Dimensional NanoBiophysical Systems
结合深度学习和粗粒度模拟方法来研究高维纳米生物物理系统
  • 批准号:
    RGPIN-2020-07145
  • 财政年份:
    2021
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Combining Deep Learning and Coarse Grained Simulation Methods to Study High-Dimensional NanoBiophysical Systems
结合深度学习和粗粒度模拟方法来研究高维纳米生物物理系统
  • 批准号:
    RGPIN-2020-07145
  • 财政年份:
    2020
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2018
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2017
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2016
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Simulating the dynamic structure of polysaccharide nanoparticles for drug attachment and delivery
模拟用于药物附着和递送的多糖纳米颗粒的动态结构
  • 批准号:
    486399-2015
  • 财政年份:
    2015
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Engage Grants Program
Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2014
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual

相似海外基金

Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2019
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2018
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2017
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2016
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
Computational Nanobiophysics: Modeling and Simulating Biomolecules in Confinement
计算纳米生物物理学:约束中生物分子的建模和模拟
  • 批准号:
    RGPIN-2014-06091
  • 财政年份:
    2014
  • 资助金额:
    $ 1.38万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了