Molecular mechanics simulations on covalent complexes of mitomycin C and its analogues with left-handed DNA duplexes.
We present molecular mechanics simulations on covalent complexes between d(GCGCGCGCGC).d(GCGCGCGCGC) in the left-handed double helical forms (B and Z) and potent antitumor antibiotics mitomycin C and three of its analogues using the all atom force field in the framework of the program AMBER(UCSF). The energy-refined models of the complexes show interesting networks of hydrogen-bonding interactions between the drugs and DNA groups in the minor groove of the left-handed helices. The energy-refined models suggest that mitomycins could bind strongly to left-handed helices. This result might be relevant to the interpretation of earlier experiments which suggested that DNA bound by mitomycin C underwent a transition to a non-Z left-handed structure.
Rao
S N
SN
Searle Research and Development, Division of G.D. Searle and Company, Skokie, Illinois 60077.
Iyengar
B S
BS
Wunz
T P
TP
Remers
W A
WA
D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D016685:Mitomycin / Q000378:metabolism*; D008937:Mitomycins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
D008937:Mitomycins; D016685:Mitomycin; D004247:DNA