Fig. 4: Computational modelling of Cyclo-(L-Trp-L-Trp) and Cyclo-(L-1-methyl-Trp-L-1-methyl-Trp) binding sites on ABCB1.

a Cyclo-(L-Trp-L-Trp) chemical structure. b Docking calculation for pairs of Cyclo-(L-Trp-L-Trp) bound to ABCB1. Two Cyclo-(L-Trp-L-Trp) molecules can bind to ABCB1. Protein is shown in cartoons while each Cyclo-(L-Trp-L-Trp) is shown in space-fill format. The first docked compound, ligand 1, is coloured orange, and the second docked compound, ligand 2, is coloured magenta. c The binding site of Cyclo-(L-Trp-L-Trp) in a Ligplot+ scheme. Corresponding residues involved in binding interactions are shown. Residues are labelled, with hydrophobic interactions indicated by red dashed arcs, and hydrogen bonds by labelled green dashed lines. d Cyclo-(L-1-methyl-Trp-L-1-methyl-Trp) chemical structure. e Docking calculation for pairs of Cyclo-(L-1-methyl-Trp-L-1-methyl-Trp) bound to ABCB1. Two Cyclo-(L-1-methyl-Trp-L-1-methyl-Trp) molecules can bind to ABCB1. Protein is shown in cartoons while each Cyclo-(L-1-methyl-Trp-L-1-methyl-Trp) is shown in space-fill format. The first docked compound, ligand 1, is coloured orange, and the second docked compound, ligand 2, is coloured magenta. f The binding site of Cyclo-(L-1-methyl-Trp-L-1-methyl-Trp) in a Ligplot+ scheme. Corresponding residues involved in binding interactions are shown. Residues are labelled, with hydrophobic interactions indicated by red dashed arcs, and hydrogen bonds by labelled green dashed lines. g ATPase assay of purified and reconstituted human ABCB1 protein with Cyclo-(L-Trp-L-Trp) and Cyclo-(L-1-methyl-Trp-L-1-methyl-Trp). The experiment was performed in triplicate, and the mean values ± S.D. are shown. Black line: Cyclo-(L-Trp-L-Trp); red line: Cyclo-(L-1-methyl-Trp-L-1-methyl-Trp).