RUI: Investigation of the structure and dynamics of type IV pilus filaments using all-atom and coarse-grained molecular dynamics

RUI:利用全原子和粗粒分子动力学研究 IV 型菌毛丝的结构和动力学

基本信息

  • 批准号:
    1817670
  • 负责人:
  • 金额:
    $ 26.61万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-06-01 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

This project will use advanced computational approaches to better understand the biomechanical properties of a protein filament that has applications ranging from bionanotechnology to cell motion and bacterial infection. Bacteria and archaea can adhere to surfaces using long, "sticky" filaments that protrude from their cell membranes called type IV pili (T4P). These filaments, which are made of thousands of copies of a protein called pilin, are incredibly strong, yet simultaneously extremely flexible. For example, a single bacterial T4P filament can support up to 10,000 times a bacterium's body weight, and T4P can be stretched to three times their original length without breaking. This project will use a computational approach known as molecular dynamics simulation to investigate the structure and dynamics of T4P filaments. Using this computational approach, simulated forces will be applied to T4P filaments to probe how they respond to being stretched, which will allow the identification of interactions that provide T4P with their great strength. The insights about T4P that will result from this work will inform applications in bionanotechnology, the role that T4P play in bacterial adhesion and motion, and will expand our general knowledge about protein filaments. Furthermore, this project will provide significant training to undergraduate students in a highly cross-disciplinary area of research at the interface of biology, physics, chemistry, and computer science. It will also develop computational learning modules and incorporate them into the undergraduate science curriculum to train students in the computational methods that are increasingly important in all scientific fields.This project uses a computation/theory-led approach to: (1) investigate the dynamics of T4P filaments from three organisms, N. gonorrhoeae, N. meningitidis, and P. aeruginosa, at the all-atom level of resolution using all-atom molecular dynamics simulation, and (2) develop coarse-grained models to study the structural properties of T4P filaments, including the structural transition that occurs for T4P under external force. This comprehensive, multi scale computational approach will provide insights into the strength and dynamics of T4P across multiple length and time scales relevant to T4P function, and importantly will bridge the gap in knowledge that currently exists between the experimental and theoretical understanding of the biomechanics of T4P filaments. Specifically, all-atom simulations will be used to characterize T4P structural heterogeneity and to identify the most important interactions between pilin subunits for maintaining T4P structural integrity in the initial stages of the polymorphic transition that T4P exhibit under the application of external force. External forces will be applied to T4P using steered molecular dynamics protocols. Additionally, all-atom and coarse-grained simulations will be used in combination to determine important T4P filament properties such as the Young's modulus, persistence length, and torsional rigidity. Finally, coarse-grained simulations of T4P filaments under force will allow for the development of the first model of the fully force-transitioned state of a T4P filament, providing unprecedented molecular-scale insights into how the filament changes shape at the molecular scale. The coarse-grained T4P model developed in this project will act as a starting model for bridging from the atomistic scale to the scale of cellular biology. This project will provide novel insights into T4P biomechanics, aid in the fundamental understanding of the role of T4P in prokaryotes, and improve understanding of the plasticity of helical biopolymers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
该项目将使用先进的计算方法来更好地了解蛋白质细丝的生物力学特性,其应用范围从生物纳米技术到细胞运动和细菌感染。细菌和古生菌可以利用从其细胞膜上伸出的长的“粘性”细丝粘附在表面上,这些细丝被称为IV型皮利(T4 P)。这些纤维由数千个名为菌毛蛋白的蛋白质拷贝组成,非常坚固,但同时也非常灵活。例如,单个细菌T4 P细丝可以支撑细菌体重的10,000倍,并且T4 P可以拉伸到其原始长度的三倍而不会断裂。该项目将使用称为分子动力学模拟的计算方法来研究T4 P细丝的结构和动力学。使用这种计算方法,模拟的力将被施加到T4 P细丝上,以探测它们对拉伸的反应,这将允许识别为T4 P提供巨大强度的相互作用。这项工作产生的关于T4 P的见解将为生物纳米技术的应用提供信息,T4 P在细菌粘附和运动中的作用,并将扩大我们对蛋白质细丝的一般知识。此外,该项目将在生物学,物理学,化学和计算机科学的接口高度跨学科的研究领域为本科生提供重要的培训。本项目采用计算/理论为主导的方法:(1)研究三种生物体(N. gonorrhoeae、淋病奈瑟菌N.脑膜炎,和铜绿假单胞菌,在全原子水平的分辨率使用全原子分子动力学模拟,和(2)开发粗粒度的模型来研究T4 P细丝的结构特性,包括T4 P在外力下发生的结构转变。这种全面的、多尺度的计算方法将在与T4 P功能相关的多个长度和时间尺度上提供对T4 P的强度和动力学的见解,并且重要的是将弥合目前存在于对T4 P细丝的生物力学的实验和理论理解之间的知识上的差距。具体而言,全原子模拟将被用来表征T4 P结构异质性,并确定最重要的菌毛蛋白亚基之间的相互作用,以保持T4 P结构的完整性,在多态性转变的初始阶段,T4 P表现出在施加外力。外力将被施加到T4 P使用转向分子动力学协议。此外,全原子和粗粒度的模拟将结合使用,以确定重要的T4 P灯丝性能,如杨氏模量,持久长度和扭转刚度。最后,粗粒度的模拟下的T4 P细丝的力将允许开发的第一个模型的完全力过渡状态的T4 P细丝,提供前所未有的分子尺度的见解细丝如何在分子尺度上改变形状。在这个项目中开发的粗粒度T4 P模型将作为从原子尺度到细胞生物学尺度的桥梁的起始模型。该项目将为T4 P生物力学提供新的见解,帮助从根本上理解T4 P在原核生物中的作用,并提高对螺旋生物聚合物可塑性的理解。该奖项反映了NSF的法定使命,并通过使用基金会的智力价值和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Three structural solutions for bacterial adhesion pilus stability and superelasticity.
  • DOI:
    10.1016/j.str.2023.03.005
  • 发表时间:
    2023-05-04
  • 期刊:
  • 影响因子:
    5.7
  • 作者:
    Doran, Matthew H.;Baker, Joseph L.;Dahlberg, Tobias;Andersson, Magnus;Bullitt, Esther
  • 通讯作者:
    Bullitt, Esther
Unveiling molecular interactions that stabilize bacterial adhesion pili.
  • DOI:
    10.1016/j.bpj.2022.04.036
  • 发表时间:
    2022-06-07
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Dahlberg, Tobias;Baker, Joseph L.;Bullitt, Esther;Andersson, Magnus
  • 通讯作者:
    Andersson, Magnus
Theory of Change to Practice: How Experimentalist Teaching Enabled Faculty to Navigate the COVID-19 Disruption
  • DOI:
    10.1021/acs.jchemed.0c00731
  • 发表时间:
    2020-09-08
  • 期刊:
  • 影响因子:
    3
  • 作者:
    Chan, Benny C.;Baker, Joseph L.;Triano, Rebecca M.
  • 通讯作者:
    Triano, Rebecca M.
{{ 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 }}

Joseph Baker其他文献

CS 224 n – Final Project
CS 224n – 最终项目
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Joseph Baker;D. Christie
  • 通讯作者:
    D. Christie
Understanding Seniors' Perceptions and Stereotypes of Aging
了解老年人对衰老的看法和刻板印象
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Sean Horton;Joseph Baker;Jean Côté;J. Deakin
  • 通讯作者:
    J. Deakin
Unveiling the Contributions of Secondary Structure and Disulfide Bonds for Bacterial Adhesion Pili Extension using a Multiscale Approach
  • DOI:
    10.1016/j.bpj.2020.11.1411
  • 发表时间:
    2021-02-12
  • 期刊:
  • 影响因子:
  • 作者:
    Joseph Baker;Tobias Dahlberg;Esther Bullitt;Magnus Andersson
  • 通讯作者:
    Magnus Andersson
Performance investigation of an electrochemical ammonia compressor stack
电化学氨压缩机组的性能研究
  • DOI:
    10.1016/j.ijrefrig.2023.05.020
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    3.9
  • 作者:
    Joseph Baker;Longsheng Cao;Y. Hwang;Chunsheng Wang;R. Radermacher
  • 通讯作者:
    R. Radermacher
Talent inclusion and genetic testing in sport: A practitioner’s guide
体育中的人才包容和基因检测:从业者指南
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Alexander B. T. McAuley;Joseph Baker;Kathryn Johnston;I. Varley;A. J. Herbert;Bruce Suraci;David C. Hughes;Loukia G Tsaprouni;A. Kelly
  • 通讯作者:
    A. Kelly

Joseph Baker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('Joseph Baker', 18)}}的其他基金

Equipment: MRI: Track 1 Acquisition of Current Hardware to Enhance Computational Research on the ELSA High Performance Computing Cluster at The College of New Jersey
设备: MRI:第一轨道采购当前硬件,以增强新泽西学院 ELSA 高性能计算集群的计算研究
  • 批准号:
    2320244
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Standard Grant
Collaborative Research: NSFGEO-NERC:Conjugate Experiment to Investigate Sources of High-Latitude Magnetic Perturbations in Coupled Solar Wind-Magnetosphere-Ionosphere-Ground System
合作研究:NSFGEO-NERC:研究太阳风-磁层-电离层-地面耦合系统中高纬度磁扰动源的共轭实验
  • 批准号:
    2027168
  • 财政年份:
    2020
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Standard Grant
MRI: Acquisition of Hardware for the Enhancement of the ELSA High Performance Computing Cluster to Enable Computational Research at The College of New Jersey
MRI:采购硬件以增强 ELSA 高性能计算集群,以支持新泽西学院的计算研究
  • 批准号:
    1828163
  • 财政年份:
    2018
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Standard Grant
Collaborative Research: SI2-SSI: Swift/E: Integrating Parallel Scripted Workflow into the Scientific Software Ecosystem
协作研究:SI2-SSI:Swift/E:将并行脚本工作流程集成到科学软件生态系统中
  • 批准号:
    1550528
  • 财政年份:
    2016
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Standard Grant
Collaborative Research: Inferring High Latitude Convection Patterns Using SuperDARN, DMSP and ACE
合作研究:使用 SuperDARN、DMSP 和 ACE 推断高纬度对流模式
  • 批准号:
    1258522
  • 财政年份:
    2014
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Continuing Grant
CAREER: Inter-Hemispheric Magnetic Conjugacy of Ionospheric Convection
职业:电离层对流的半球间磁共轭
  • 批准号:
    1150789
  • 财政年份:
    2012
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Continuing Grant
GEM Postdoc: Characteristics of Ultra Low Frequency (ULF) Waves Associated with Electron Acceleration to Relativistic Energies
GEM 博士后:与电子加速相对论能量相关的超低频 (ULF) 波的特征
  • 批准号:
    0924919
  • 财政年份:
    2009
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Standard Grant
Technology Transfer For Energy Management
能源管理技术转让
  • 批准号:
    7501767
  • 财政年份:
    1975
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Standard Grant

相似海外基金

Investigation on the Sub-structure development in HSA6 alloys to maximise strength via Thermomechanical simulations
通过热机械模拟研究 HSA6 合金的子结构开发以最大限度地提高强度
  • 批准号:
    2901174
  • 财政年份:
    2024
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Studentship
Development of atomically precise nano-molecular composite for investigation and exploration of their structure and properties
开发原子级精确的纳米分子复合材料,用于研究和探索其结构和性能
  • 批准号:
    23H01917
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Investigation on detection of terahertz waves using metallic magnetic/non-magnetic ultra-thin film hetero-structure
金属磁性/非磁性超薄膜异质结构探测太赫兹波的研究
  • 批准号:
    23K03957
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Investigation of UBQLN2 in neuronal dysfunction and ALS-FTD
UBQLN2 在神经元功能障碍和 ALS-FTD 中的研究
  • 批准号:
    10638277
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
Investigation of a novel ventral pallidum population expressing corticotropin-releasing factor receptor 1
表达促肾上腺皮质激素释放因子受体 1 的新型腹侧苍白球群体的研究
  • 批准号:
    10677069
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
Mechanistic investigation into Frizzled-2 signaling for treatment of Osteogenesis Imperfecta
Frizzled-2 信号传导治疗成骨不全症的机制研究
  • 批准号:
    10680236
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
Neuromelanin MRI: A tool for non-invasive investigation of dopaminergic abnormalities in adolescent substance use.
神经黑色素 MRI:一种用于非侵入性调查青少年物质使用中多巴胺能异常的工具。
  • 批准号:
    10735465
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
Establishing foundational tools and datasets for investigation of NSD1 gene function in neural development
建立用于研究神经发育中 NSD1 基因功能的基础工具和数据集
  • 批准号:
    10711291
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
Intracranial Investigation of Neural Circuity Underlying Human Mood
人类情绪背后的神经回路的颅内研究
  • 批准号:
    10660355
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
A mixed-methods investigation of parental burden and adolescent service use following discharge from psychiatric hospitalization
精神病院出院后父​​母负担和青少年服务使用的混合方法调查
  • 批准号:
    10748684
  • 财政年份:
    2023
  • 资助金额:
    $ 26.61万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了