| 项目编号: | 1605167
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| 项目名称: | Rapid screening of biomolecular conformation and binding interactions |
| 作者: | Victor Ugaz
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| 承担单位: | Texas A&M Engineering Experiment Station
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| 批准年: | 2016
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| 开始日期: | 2016-06-01
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| 结束日期: | 2019-05-31
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| 资助金额: | 300000
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | macromolecular conformation
; conformational change
; v. rapid screening
; biomolecular conformation
; nanoscale conformation
; rapid parallel screening
; high throughput screening
; protein
; binding interactionsthis fundamental research project
; protein-based binding species
; binding interaction
; different binding mode
|
| 英文摘要: | CBET 1605167 Ugaz, V.
Rapid screening of biomolecular conformation and binding interactions
This fundamental research project will develop a new tool for biological separations that will make it possible to image the nanoscale conformation of biomacromolecules (e.g. DNA, RNA, proteins) much smaller in size than can currently be probed. This platform will be robust and amenable towards automation. This project will deliver innovative capabilities that are needed to support high throughput screening of compounds with advanced chemical and biochemical functions (e.g., therapeutic targets). The project approach imposes no lower limit on the size of macromolecules that can be interrogated and can be performed within a 10 to 20 minute experiment, enabling orders of magnitude higher throughput than currently possible. More broadly, the fundamental physical underpinnings that make this analysis possible will be used in a tablet-based computer format, enabling general audiences to access and to interact with nanoscale physics in a fun and engaging way that mirrors familiar tablet games.
The principal investigator will conduct fundamental research that is aimed at establishing an innovative entropic force microscope capable of quantitatively mapping conformational changes in biomacromolecules (e.g. DNA, RNA, proteins), both self-induced and emerging from complexation with binding agents (e.g. small molecules, proteins, adducts). A slate of small molecule and protein-based binding species will be evaluated encompassing different binding modes to quantify their influence on macromolecular conformation. A predictive model will also be developed to inform the rational selection of tailored nanoporous hydrogel formulations and polymerization conditions, enabling macromolecular conformation to be optimally probed within a broad range of analyte size. This work will lay a foundation to establish a new tool capable of performing rapid parallel screening of binding interactions in a highly automated fashion not possible using existing methods. More broadly, a conventional Brownian dynamics simulation toolbox will be implemented into an iPad application that provides a visual representation of polymer coil size, relaxation phenomena, Brownian motion, and transport under an external driving force (i.e., electrophoresis). The app will harness the embedded 2D physics engine employed by popular video games, making the simulation toolbox accessible and engaging in a way that is challenging to achieve by presenting the physics alone. Finally, the project will train and mentor a Ph.D. student and undergraduate and senior high school students will be recruited from underrepresented groups in STEM for research experiences. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/92300
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| Appears in Collections: | 全球变化的国际研究计划
科学计划与规划
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| Recommended Citation: | |
Victor Ugaz. Rapid screening of biomolecular conformation and binding interactions. 2016-01-01.
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