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Long Time-Scale Atomistic Simulations of the Structure and Dynamics of Transcription Factor-DNA Recognition

submitted on 23.12.2018, 14:17 and posted on 26.12.2018, 15:18 by Qinghua Liao, Malin Lüking, Dennis M. Krüger, Sebastian Deindl, Johan Elf, Peter M. Kasson, Shina Caroline Lynn Kamerlin
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Recent years have witnessed an explosion of interest in computational studies of DNA binding proteins, including both coarse grained and atomistic simulations of transcription factor-DNA recognition, in order to understand how these transcription factors recognize their binding sites on the DNA with such exquisite specificity. The present study performs μs-timescale all-atom simulations of the dimeric form of the lactose repressor (LacI), both in the absence of any DNA, and in the presence of both specific and non-specific complexes, considering three different DNA sequences. We examine, specifically, the conformational differences between specific and non-specific protein-DNA interactions, as well as the behavior of the helix-turn-helix motif of LacI when interacting with the DNA. Our simulations suggest that stable LacI binding occurs primarily to bent A-form DNA, with a loss of LacI conformational entropy and optimization of correlated conformational equilibria across the protein. In addition, binding to the specific operator sequence involves a slightly larger number of stabilizing DNA-protein hydrogen bonds (in comparison to non-specific complexes), that may account for the experimentally observed specificity for this operator. In doing so, our simulations provide a detailed atomistic description of potential structural drivers for LacI selectivity.


Knut and Alice Wallenberg Foundation (KAW 2016.0077)

Swedish Research Council (VR Environment Grant, 2016- 06213)


Email Address of Submitting Author


Uppsala University



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest.

Version Notes

Non-peer reviewed first version.