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

亚利桑那州立大学的Arjan Van Der Vaart获得了理论和计算化学项目的CAREER奖，从事模拟序列特异性dna结合（SSDB）蛋白质构象结合动力学的计算方法的开发研究。分子动力学模拟被用于研究序列特异性DNA结合蛋白的耦合DNA结合-蛋白质折叠（或展开）。目前的研究主要集中在DNA结合时部分折叠的lac抑制因子头部和部分展开的Ets-1转录因子。新的分析方法和偏置算法正在与粗粒度模型一起开发，以计算转换路径。将模拟结果与实验结果进行了比较，并提出了具体的突变实验。该项目的目的是阐明SSDB蛋白触发主要细胞事件机制的关键步骤。这项工作对我们理解重要的生物化学事件有着广泛的影响。Van Der Vaart参与了一项针对高中教师的浸入式研究项目，旨在为高中学生开发教学模块，从而产生了进一步的影响。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，并让他们参与暑期本科生研究项目，进一步扩大了他的项目的影响。

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.