Theoretical Investigations of Dynamic Aspects of Protein-DNA Interactions

蛋白质-DNA 相互作用动态方面的理论研究

基本信息

批准号：
1664218
负责人：
Anatoly Kolomeisky
金额：
$ 43.5万
依托单位：
William Marsh Rice University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1664218&HistoricalAwards=false
关键词：
Theoretical Investigations Dynamic Aspects Protein

项目摘要

Anatoly Kolomeisky of William Marsh Rice University is supported by an award from the Chemical Theory, Models and Computational Methods Program in the Chemistry Division to theoretically investigate interactions between two major classes of biological molecules: DNA and proteins. This project is co-funded by the Molecular Biophysics Program in the Molecular and Cellular Biosciences Division. DNA encodes the genetic plans for all living organisms. Proteins read this information and implement it in the cell. Proper timing is a key aspect of protein-DNA interactions due to the dynamic nature of living cells. If the proper interactions do not occur at the right time, the entire biological system can fail catastrophically. Understanding protein-DNA interactions can lead to new insights for drug discovery and contribute to technological breakthroughs such as bio-inspired or biomimetic materials. Professor Kolomeisky is combining theoretical modeling, simulation, and bioinformatics to understand the molecular foundations of the temporal dependence and efficiency of protein-DNA interactions. Specific questions include: how proteins identify the correct DNA binding sites in performing their functions; the effects of DNA loop formation on multi-site proteins that can bind at different DNA sites; mechanisms of DNA editing using the newly-discovered CRISPR associated protein technology; and understanding the tradeoff between strong binding and fast recognition in determining how proteins bind to DNA. Close collaborations with experimental and theoretical groups will enable testing of the new models, and promote a deeper understanding of these complex natural processes. Professor Kolomeisky is providing opportunities for high school and undergraduate students from underrepresented groups to participate in this research and gain valuable training and experience for their future careers. Outreach activities include a high-school scientific projects competition, co-organization of an undergraduate chemistry research symposium, public lectures delivered at venues such as the Rice Science Café, and continued collaboration with the Rice robotics systems lab to create online games based on the results of this research.This project focuses on developing a theoretical program to analyze the temporal dependence of protein-DNA interactions. These fundamental interactions are analyzed using a variety of theoretical tools including discrete-state stochastic models, first-passage analysis, bioinformatics methods and extensive Monte Carlo computer simulations. The advantage of this multiscale approach is that it takes into account in a consistent manner the major physical and chemical properties of DNA and proteins interacting in the complex cellular environment. In collaboration with experimental research groups, theoretical predictions are tested using various techniques, including single-molecule spectroscopy, chemical kinetics, and bioinformatic analysis. An outreach program developed by Professor Kolomeisky provides the opportunity for local high-school students and undergraduate students from underrepresented minority groups to participate in scientific research in an academic setting. The project also highlights the benefits of science for society by directly presenting scientific findings to the local community in the informal setting of café discussions, as well as communicating with science writers in local newspapers and participating in scientific Internet blog discussions. The broader impacts of this project include a multidisciplinary training program for young researchers of different levels that will prepare them better for future technological and industrial challenges.

William Marsh大米的Anatoly Kolimeisky得到了化学理论，模型和计算方法的奖励，而化学分裂是由两个主要类别的生物分子之间的理论上相互作用的。 d。当时，整个生物系统会导致灾难性的动作。蛋白质-DNA相互作用的效率。在确定蛋白质与实验和理论意志的紧密合作时，将使对这些复杂的自然过程有更深入的了解培训和经验为他们的未来职业外展活动培训高科学项目竞赛，在稻米科学咖啡馆进行的本科化学研究公开讲座的共同组织，并继续与Rice Robotics Systems Lab合作以基于Crine Game S的这项研究的结果。该项目的重点是蛋白质-DNA相互作用的时间范围。在复杂的细胞环境中，DNA和蛋白质相互作用的CAL和化学性质中考虑了。 - 学校的学生和地下学生来自代表性的少数群体，参加了祖先的科学研究，该项目还向当地社区的科学研究结果强调了非正式的咖啡馆讨论。参与科学互联网博客。