Figure 4.

Blind docking of fatty acids into the molecular model of TrwD. Blind docking predictions between a molecular model of monomeric TrwD and fatty acid ligands (palmitic acid (PALM) and 2-bromopalmitic acid (2-BR-PALM)) were performed using the EADock dihedral spacing sampling engine of the SwissDock server (32). Both fatty acids fit into a pocket located at the interface between the NTD (pink) and the linker region (light orange), which connects the NTD with the catalytic CTD (brown). The top left and right panels correspond to the same view in cartoon and surface representation, respectively. The carbon chains of both fatty acids have a similar orientation (blue and yellow for palmitic acid and 2-bromopalmitic acid, respectively). However, the carboxylic group of the 2-bromo derivative is buried in a pocket formed by the NTD and the linker domain of the protein, being the bromine atom (dark green) stabilized by electrostatic basic residues located in the region. On the contrary, the carboxylic group of the palmitic acid (red) is 120° apart, out of the linker region. The right panel shows a zoom of the binding pocket, in which the basic residues surrounding the carboxylic groups of the fatty acids are better appreciated. For more clarity, see also Movie S1.