Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Long Time-Scale Atomistic Simulations of the Structure and Dynamics of Transcription Factor-DNA Recognition
Ist Teil von
The journal of physical chemistry. B, 2019-05, Vol.123 (17), p.3576-3590
Ort / Verlag
United States: American Chemical Society
Erscheinungsjahr
2019
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
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, to understand how these transcription factors recognize their binding sites on the DNA with such exquisite specificity. The present study performs microsecond time scale 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 nonspecific complexes, considering three different DNA sequences. We examine, specifically, the conformational differences between specific and nonspecific 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 nonspecific complexes), which 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.