Molecular Dynamics Study of DNA Duplex Containing Carbazole-derived Universal Base

摘要

Universal base is a man-made residue that can be incorporated into the DNA double strands without any discrimination against natural bases (A, C, G, T). The MD simulations with AMBER99 force field were employed to investigate the structure and dynamics of the modified 15-mer DNA duplexes containing carbazole-derived universal bases: carbazole (CBZ), 3,6-dicyanocarbazole (DCC), 3,6-dinitrocarbazole (DNC), and 3-nitro-6-cyanocarbazole (NCC), where X = CBZ, DCC, DNC, or NCC, respectively. The RMSD and B-factor of the modified DNAs backbones around the universal base unit fluctuate more than the reference sequence in the same position. The thermodynamic parameter for duplex stability was estimated by using MM-PBSA method. The averaged duplex formation free energy (△G) of all modified DNAs exhibited that the stability order was approximately DNC>NCC>CBZ>DCC, which differed from the reference sequence exceptional DNC unit. The averaged △G value of the DNC unit is very close to that of the reference sequence. This calculation indicated that the DNC unit can be considered as a good candidate for using as a universal base.