Figure 4

The atomic correlation heat map (A,B) by amino acid residues of MD simulation using apo PFKFB3, and the dynamically correlated regions under different scenario (B–D). (A) is the correlation heat map by residues of a PFKFB3 monomer of the apo structure. The box and the zoomed-in sub-plot show the three weakly correlated α-helices highlighted in (B) (α1 in orange, α17 in cyan, and α18 in yellow). The double-headed arrow in A shows the relatively stronger correlations of the autoregulatory domain (β-hairpin) to the Glu322-Ala325 loop (dark blue) through part of the α17-helix (Tyr362-Arg378, cyan). The β-hairpin (in red)-to-phosphatase correlated regions through α17 (cyan) are illustrated in (C). In (D), the docked pose of compound 6 (pink) indicates that the peptide is interfering with E322-A325 loop (dark blue) through the α17-helix (cyan). The enzyme substrates are all shown in green in (B–D).