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

亚利桑那州州立大学的Arjan货车Der Vaart获得了理论和计算化学计划的CAREER奖的支持，以开展模拟序列特异性DNA结合（SSDB）蛋白质构象结合动力学的计算方法开发研究。分子动力学模拟正在进行研究耦合的DNA结合-蛋白质折叠（或解折叠）-序列特异性DNA结合蛋白。 这些研究集中在乳糖阻遏物的头部部分折叠和Ets-1转录因子的DNA结合后部分展开。 新的分析方法和偏置算法正在沿着一个粗粒化的模型来计算过渡途径。 这些模拟的结果进行了比较，实验和具体的突变实验，然后建议。 该项目的目的是阐明SSDB蛋白触发主要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物化学事件产生了广泛的影响。 通过货车Der Vaart参与旨在为高中学生开发教学模块的高中教师沉浸式研究方案，它正在产生进一步的影响。 货车德·法特正在通过招募和指导来自代表性不足的少数群体的学生，并让他们参与暑期本科生研究项目，进一步扩大他的项目的影响。

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.