A theoretical exploration of conformational aspects of ethidium bromide intercalation into a d(CpG)2 minihelix

✍ Scribed by Kai-Xian Chen; Nohad Gresh; Bernard Pullman

• Book ID: 102761214
• Publisher: Wiley (John Wiley & Sons)
• Year: 1987
• Tongue: English
• Weight: 969 KB
• Volume: 26
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360260605

✦ Synopsis

In order to gain insight into the structural and conformational factors involved in the binding of ethidium bromide to oligonucleotides, theoretical computations are performed on the ethidium bromide-d(CpG)2 complexes, in which the ligand-nucleotide interaction energy, the conformational energy of the ligand, and that of the nucleotide are simultaneously optimized. The intermolecular and conformational energy computations are performed with the SIBFA procedures (sum of interactions between fragments computed ab initio), which use empirical formulas based on ab initio SCF (Self Consistent Field) computations. The conformations of the intercalation site are generated by the AGNAS procedure (algorithm to generate nucleic acid structure) elaborated by Miller and co-workers. The pyrimidine sugar is held in the C3'-endo conformation and the purine sugar in the C2'-endo conformation in conformity with both x-ray and nmr results for dinucleoside duplexes. Several candidate intercalation sites, selected on the basis of energy criteria, could be generated by the procedure. They were found to recur in a persistent fashion over the whole range of unwinding angles investigated, which span from -20' to -30". Among these, a conformation closely similar to the one determined crystallographically by Sobell et al. was found to be the intrinsically most favorable and to react with the strongest interaction energy with ethidium. For this conformation, the most favorable value of the unwinding angle is -26", close to the value in the crystal structure. Several painvise correlations of structural parameters could be evidenced. The effect of the 2'OH groups (as in RNA duplexes as opposed to DNA duplexes) was also investigated and shown to further enhance, albeit slightly, the intrinsic stability of the Sobell-like Aa = -26' conformation.