Sequential binding pocket opening when warfarin accesses its binding site. The profile of the minimum distances between the hydrophobic paired leucine residues (L15:L111, L15:L128, and L22:L105) that help sustain a stable VKOR structure are recorded during the 448-picosecond steered MD simulation (bottom). Snapshots of warfarin inside VKOR at the indicated time points are shown (insets). Key residues, encountered during warfarin’s accessing the binding site in VKOR, are labeled and displayed using stick diagrams. Minimum distances between paired lysine residues are labeled.