Figure 6: Structure-based lead identification for the inhibition of MtbHU–DNA interaction.
From: Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors
SD1 and SD4 screened using Virtual Screening Workflow (Schrödinger Discovery Tool). (a) SD1 (PubChem CID: 5821513), a trans-stilbene derivative. (b) Energy-minimized model of SD1 bound to the protein based on the GLIDE dock-pose. In the figure, hydrogen bond interactions between SD1 and the positively charged residues Arg55, 58, 80 and Lys86 of MtbHUN are shown. The same residues are also involved in electrostatic interactions, see text for details. (c) Inhibition of MtbHU–DNA binding by SD1 and its corresponding inhibition curve (inset, IC50 value). (d) SD4, a methoxy derivative of SD1. (e) Energy-minimized model of SD4 bound to the protein based on the GLIDE dock-pose. In the figure, hydrogen bond interactions between SD4 and the positively charged residues Arg55, 58, 80 and Lys86 of MtbHUN are shown. The same residues are also involved in electrostatic interactions, see text for details. (f) Inhibition of MtbHU–DNA binding by SD4 and its corresponding inhibition curve (inset, IC50 value).
