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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

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.