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

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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.