Fig. 8: Suggested modifications of berberine enabling additional interaction with the KRAS-G4.

The black circles indicate the positions to be modified by introducing side chains for groove interactions. The black arrows show the grooves at 5′- and 3′-sites where the attached side chain will locate. The red circle suggests the positions to introduce hydrogen bonds between berberine and thymine T10. The KRAS-G4 is shown in cartoon representation. Cyan, guanine; magenta, adenine; blue, thymine; orange, cytosine; yellow, berberine.