The binding poses for warfarin on VKORC1 and VKORC1L1. (A) Favored docking pose of warfarin on VKORC1L1 (gray-colored ribbon format). The electrostatic surface charge distribution is illustrated based on columbic charge distribution (blue, positive charge; red, negative charge). The clustered arginines on the endoplasmatic reticulum (ER) luminal loop are depicted in blue and warfarin in beige-colored stick forms. (B) Favored docking pose of warfarin on VKORC1 (green-colored ribbon format). Charge distribution, arginines, and warfarin are colored as in panel A. (C) Interactions of the bound warfarin (beige stick form) with arginine residues (blue-colored stick forms) of VKORC1L1 (gray-colored ribbon format). Hydrophobic interactions between warfarin and VKORC1L1 residues are depicted as green lines, and charge-based (cation-π) interactions are depicted with blue lines of different intensities. (D) Structural alignment of the VKORC1 and VKORC1L1 models. The backbone of the VKORC1 and VKORC1L1 models are colored as in panels A and B. The arginine residues clustered around the favored warfarin binding site of each model are depicted in stick format. Opposite drug binding sites are highlighted with shaded triangles (gray for VKORC1L1, green for VKORC1).