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BioCARS: Structural Dynamics and Biological Mechanisms

BioCARS：结构动力学和生物机制

基本信息

批准号：
10093063
负责人：
JOHN Keith MOFFAT
金额：
$ 128.97万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10093063
关键词：
Address Algorithms Area Automobile Driving Biological Biological Process Catalysis Characteristics Charge Collaborations Communities Complex Coupled Crystallization Crystallography Data Data Analyses Data Set Development Devices Disease Educational workshop Engineering Environment Enzymes Experimental Designs General Population Goals Image Improve Access Knowledge Laboratories Measurement Methods Microfluidics Modernization Molecular Molecular Conformation Motion Pharmacology Photons Physiological Printed Media Process Proteins Regulation Resolution Roentgen Rays Sampling Science Services Signal Transduction Software Tools Source Structure Synchrotrons System Technology Temperature Therapeutic Time Training Update Work X ray diffraction analysis X-Ray Crystallography base chemical reaction computerized data processing design detector electric field experimental study high school interest macromolecule meetings new technology next generation novel novel strategies open source posters practical application prospective research and development research facility symposium technology development technology research and development time use tool transmission process undergraduate student

项目摘要

Abstract A major goal is biomedical science is to move beyond static images of proteins and other biological macromolecules to the internal dynamics underlying their function. This level of study is necessary to understand how these molecules work, to engineer new functions, and to rationally develop therapeutics. In this application, we propose two technological research and development projects that take advantage of the special characteristics of the BioCARS national synchrotron facility to address these goals. In the first, TR&D 1, we describe time-resolved serial micro-crystallography (TR-SMX) coupled with initiation of chemical reactions within molecules. This approach is enabled by the high intensity and tight focusing of X-rays at BioCARS, the availability of a large area, fast detectors, and the use of novel crystal injectors and microfluidic mixers. TR- SMX enables users to observe the dynamics of molecules as they execute their biological function at physiological temperatures. In the second, TR&D 2, we describe electric field-stimulated X-ray crystallography (EFX), a new method visualizing conformational changes within proteins and other biological macromolecules. This method uses external electric fields to induce global, subtle motions of atoms within proteins, with readout using time-resolved X-ray diffraction. Initial work demonstrates the practical application of EFX, and confirms the ability to globally excite motions throughout a protein molecule, including those of biological relevance. Since charges and dipoles are universally present in macromolecules, EFX represents, in principle, a general approach for intramolecular dynamics. We describe several user-based driving biomedical projects and collaborative and service projects that cover a wide range of important problems and push both technologies. User training and active approaches to dissemination to both expert and non-expert, wider audiences will enable broad use of the new technologies by the scientific community.

摘要生物医学科学的一个主要目标是超越蛋白质和其他生物物质的静态图像，大分子与其功能背后的内部动力学之间的关系。这种程度的学习是必要的，了解这些分子如何工作，设计新的功能，并合理开发治疗方法。在本申请，我们提出了两个技术研究和开发项目，利用 BioCARS国家同步加速器设施的特殊特性来实现这些目标。在第一个，TR&D 1，我们描述了时间分辨连续微晶体学（TR-SMX）与化学反应引发相结合在分子中。这种方法是由BioCARS的高强度和紧密聚焦的X射线实现的，大面积、快速检测器的可用性，以及新型晶体注射器和微流体混合器的使用。TR- SMX使用户能够观察分子在执行其生物功能时的动力学，生理温度。在第二部分TR& D2中，我们描述了电场激发的X射线晶体学 (EFX)这是一种可视化蛋白质和其他生物大分子构象变化的新方法。这种方法使用外部电场来诱导蛋白质内原子的全局微妙运动，使用时间分辨X射线衍射。初步工作表明，EFX的实际应用，并确认在整个蛋白质分子中全局激发运动的能力，包括那些与生物学相关的运动。由于电荷和偶极子普遍存在于大分子中，因此EFX原则上代表一般的分子内动力学方法。我们描述了几个基于用户的驱动生物医学项目，合作和服务项目，涵盖广泛的重要问题，并推动两种技术。用户培训和向专家和非专家传播的积极做法，将使更多的受众使科学界能够广泛使用新技术。

项目成果

期刊论文数量（35）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Microsecond dynamics control the HIV-1 Envelope conformation.

DOI：
10.1126/sciadv.adj0396
发表时间：
2024-02-02
期刊：
SCIENCE ADVANCES
影响因子：
13.6
作者：
Bennett, Ashley L.;Edwards, Robert;Kosheleva, Irina;Saunders, Carrie;Bililign, Yishak;Williams, Ashliegh;Bubphamala, Pimthada;Manosouri, Katayoun;Anasti, Kara;Saunders, Kevin O.;Alam, S. Munir;Haynes, Barton F.;Acharya, Priyamvada;Henderson, Rory
通讯作者：
Henderson, Rory

Microbial production of megadalton titin yields fibers with advantageous mechanical properties.

DOI：
10.1038/s41467-021-25360-6
发表时间：
2021-08-30
期刊：
Nature communications
影响因子：
16.6
作者：
Bowen CH;Sargent CJ;Wang A;Zhu Y;Chang X;Li J;Mu X;Galazka JM;Jun YS;Keten S;Zhang F
通讯作者：
Zhang F

Resolving conformational changes that mediate a two-step catalytic mechanism in a model enzyme.

解决模型酶中介导两步催化机制的构象变化。

DOI：
10.1101/2023.06.02.543507
发表时间：
2023
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Greisman,JackB;Dalton,KevinM;Brookner,DennisE;Klureza,MargaretA;Sheehan,CandiceJ;Kim,In-Sik;Henning,RobertW;Russi,Silvia;Hekstra,DoekeR
通讯作者：
Hekstra,DoekeR

Axial vs equatorial: Capturing the intramolecular charge transfer state geometry in conformational polymorphic crystals of a donor-bridge-acceptor dyad in nanosecond-time-scale.