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: 1007816
• 负责人: Arjan Van Der Vaart
• 金额: $ 57.19万
• 依托单位: University of South Florida
• 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: 2009-10-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1007816&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得到了理论和计算化学计划颁发的职业奖的支持，该计划致力于研究开发计算方法来模拟序列特异性DNA结合(SSDB)蛋白质的构象结合动力学。分子动力学模拟正在被用来研究序列特异性DNA结合蛋白的耦合DNA结合--蛋白质折叠(或去折叠)。研究的重点是部分折叠的乳胶抑制物头盔和部分解开DNA结合的Ets-1转录因子。正在开发新的分析方法和偏置算法，以及计算过渡路径的粗粒度模型。将这些模拟的结果与实验进行比较，然后建议进行特定的突变实验。该项目的目的是阐明SSDB蛋白触发重大细胞事件的机制中的关键步骤。这项工作对我们理解重要的生化事件产生了广泛的影响。通过Van Der Vaart参与一个高中教师研究浸入式方案，它正在产生进一步的影响，该方案旨在为高中生开发教学模块。Van Der Vaart正在通过招募和指导来自代表性不足的少数群体的学生，并让他们参与夏季本科生研究项目，进一步扩大他的项目的影响。