Conformational Dynamics of the Partially Disordered Yeast Transcription Factor GCN4

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• 作者：Paul Robustelli ; Nikola Trbovic ; Richard A. Friesner ; Arthur G. Palmer ; III
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2013
• 出版时间：November 12, 2013
• 年：2013
• 卷：9
• 期：11
• 页码：5190-5200
• 全文大小：464K
• 年卷期：v.9,no.11(November 12, 2013)
• ISSN：1549-9626

文摘

Molecular dynamics (MD) simulations have been employed to study the conformational dynamics of the partially disordered DNA binding basic leucine zipper domain of the yeast transcription factor GCN4. We demonstrate that back-calculated NMR chemical shifts and spin-relaxation data provide complementary probes of the structure and dynamics of disordered protein states and enable comparisons of the accuracy of multiple MD trajectories. In particular, back-calculated chemical shifts provide a sensitive probe of the populations of residual secondary structure elements and helix capping interactions, while spin-relaxation calculations are sensitive to a combination of dynamic and structural factors. Back-calculated chemical shift and spin-relaxation data can be used to evaluate the populations of specific interactions in disordered states and identify regions of the phase space that are inconsistent with experimental measurements. The structural interactions that favor and disfavor helical conformations in the disordered basic region of the GCN4 bZip domain were analyzed in order to assess the implications of the structure and dynamics of the apo form for the DNA binding mechanism. The structural couplings observed in these experimentally validated simulations are consistent with a mechanism where the binding of a preformed helical interface would induce folding in the remainder of the protein, supporting a hybrid conformational selection/induced folding binding mechanism.