CAREER: Molecular dynamics simulations of the conformational binding dynamics of sequence-specific DNA-binding proteins

职业：序列特异性 DNA 结合蛋白构象结合动力学的分子动力学模拟

• 批准号: 0846161
• 负责人: Arjan Van Der Vaart
• 金额: $ 60万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0846161&HistoricalAwards=false
• 关键词: CAREER; Molecular; dynamics; simulations; conformational

Arjan Van Der Vaart of Arizona State University is supported by a CAREER award from the Theoretical and Computational Chemistry program to carry out research on the development of computational methods for simulating conformational binding dynamics of sequence-specific DNA-binding (SSDB) proteins. Molecular dynamics simulations are being carried out to study the coupled DNA binding - protein folding (or unfolding) - of sequence-specific DNA-binding proteins. The studies are focusing on the lac repressor headpiece which partially folds and the Ets-1 transcription factor which partially unfolds upon DNA binding. New analysis methods and biasing algorithms are being developed along with a coarse-grined model to compute transition pathways. The results of these simulations are compared to experiment and specific mutation experiments are then suggested. The aim of the project is to elucidate the key step in the mechanism by which SSDB proteins trigger major cellular events.The work is having a broad impact on our understanding of important biochemical events. It is having a further impact through the participation of Van Der Vaart in a research immersion program for high school teachers which aims to develop teaching modules for high school students. Van Der Vaart is further broadening the impact of his project by recruiting and mentoring students from under-represented minority groups and involving them in summer undergraduate research projects.

亚利桑那州立大学的Arjan van der vaart获得了理论和计算化学计划的职业奖，旨在进行开发计算方法的研究，以模拟序列特异性DNA结合（SSDB）蛋白的构象结合动力学。正在进行分子动力学模拟，以研究序列特异性DNA结合蛋白的耦合DNA结合 - 蛋白折叠（或展开）。 这些研究集中在部分折叠的LAC阻遏头和DNA结合后部分展开的ETS-1转录因子上。 新的分析方法和偏置算法正在开发与粗略的模型一起计算过渡途径。 将这些模拟的结果与实验进行了比较，然后提出了特定的突变实验。 该项目的目的是阐明SSDB蛋白触发主要细胞事件的机制的关键步骤。这项工作对我们对重要生化事件的理解产生了广泛的影响。 通过范德·瓦特（Van der Vaart）在一项针对高中教师的研究浸入计划中，它旨在为高中生开发教学模块，从而产生进一步的影响。 Van der Vaart通过招募和指导来自代表性不足的少数群体的学生并参与夏季的本科研究项目，进一步扩大了其项目的影响。