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Comment
. 2022 Oct 18;121(20):3765-3767.
doi: 10.1016/j.bpj.2022.09.020. Epub 2022 Sep 21.

It is in the flanks: Conformational flexibility of transcription factor binding sites

Tsu-Pei Chiu  1 , Jinsen Li  1 , Yibei Jiang  1 , Remo Rohs  2
Affiliations
Comment

It is in the flanks: Conformational flexibility of transcription factor binding sites

Tsu-Pei Chiu et al. Biophys J. .
No abstract available

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1
Figure 1
Conformational flexibility of Hox-DNA binding sites. (A) Overview of a co-crystal structure of an Exd-Hox complex, with Scr and the DNA target site 5′-TAAGATTAATCGG-3′ (PDB: 2R5Z). (B) DNA minor groove width profiles as a function of nucleotide position for Exd-Scr bound complexes in both panels. The minor groove width profiles are derived from all-atom MD trajectories, with Scr preferred binding site 5′-CTCTAAGATTAATCGGCTG-3′ (upper panel) and Ubx preferred binding site 5′-CTCTATGATTTATGGGCTG-3′ (lower panel). AMBER force fields (AMBER94 for nucleic acids and AMBER99SB for proteins) (11) were used for the MD simulations. DNA shape parameters were computed with CURVES (12) for MD snapshots every 100 ps using Trj2Shape (13). (C) Violin plots directly comparing R2 values between sequence + static shape models (white) and shape fluctuation-augmented models (gray) for two different models consisting of sequence and either 4 or 13 DNA shape features (14). Models were trained by L2-regularized multiple linear regression using 10-fold cross validation on 21 datasets derived from SELEX-seq experiments for the Hox TF family (14). Statistical significance upon adding conformational flexibility to the models in form of standard deviation (SD) of DNA shape features is indicated by ∗∗∗∗ representing p < 0.0001.
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References

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