Comparison of the incremental and hierarchical methods for crystalline neon.

We present a critical comparison of the incremental and hierarchical methods for the evaluation of the static cohesive energy of crystalline neon. Both of these schemes make it possible to apply the methods of molecular electronic structure theory to crystalline solids, offering a systematically improvable alternative to density functional theory. Results from both methods are compared with previous theoretical and experimental studies of solid neon and potential sources of error are discussed. We explore the similarities of the two methods and demonstrate how they may be used in tandem to study crystalline solids.

C8-guanine adduct-induced stabilization of a -1 frame shift intermediate in a nonrepetitive DNA sequence.

The mechanism of frame shift mutagenesis induced by N-(deoxyguanosin-8-yl)-1-aminopyrene, the major DNA adduct formed by the carcinogen 1-nitropyrene, was investigated by thermal melting studies of a 13-mer in which the adduct was flanked by a 5' and a 3' C. Compared to the unmodified 13-mer, the adduct destabilized the duplex by 4-5 kcal/mol, and the DeltaDeltaG value remained approximately the same regardless of which base was placed opposite the adduct. In contrast, deletion of the base opposite the adduct stabilized the duplex by nearly 4 kcal/mol. The adduct in the same sequence context was inserted into a bacteriophage M13 DNA containing the simian virus 40 origin of replication. The constructed DNA template was replicated in vitro with extracts from normal human fibroblasts. The adduct was not removed from the progeny DNA following bidirectional semiconservative replication, which suggests that it had been bypassed, rather than repaired, by the cell extract. When newly replicated bacteriophage was evaluated for mutations in the region of the modified G, most contained a G at the adduct site, indicating error-free replication. A small number of mutants ( approximately 2 x 10(-3)) were detected, all of which contained a targeted G.C base pair deletion. This suggests a relationship between the thermodynamic stability of the adduct in DNA and the errors that occurred during replicative bypass by the human DNA polymerases.

Solution properties and computational analysis of an oligodeoxynucleotide containing N-(deoxyguanosin-8-yl)-1-aminopyrene.

An oligodeoxyribonucleotide 5'-d(CTCATGAPATTCC), in which G(AP) denotes N-(guanin-8-yl)-1-aminopyrene, the C8-guanine adduct of reductively activated 1-nitropyrene, was synthesized and characterized by polyacrylamide gel electrophoresis, absorption and fluorescence spectroscopy, circular dichroism, and thermal melting studies. Polyacrylamide gel electrophoresis showed slower mobility of the adducted oligonucleotide in single-stranded form compared to its unmodified counterpart, as expected. In duplex form, however (with a deoxycytidine opposite the adduct), the adducted 11mer migrated faster than the parent duplex. Absorption and fluorescence studies indicated significant interaction of the aminopyrene residue with the DNA bases in the modified 11mer. The spectroscopic data also suggested the presence of one or more conformers in which the aminopyrene residue is quasi-intercalative, as well as one(s) in which the aminopyrene is externally bound. Thermodynamic parameters for the helix-to-coil transitions for the 11mer duplex were determined. The difference in free energy (delta delta G degree) between the unmodified and modified sequences was relatively small (approximately 1.2 kcal/mol). Circular dichroism spectra indicated the presence of essentially B-form DNA. The energy minimizations suggested that the most stable conformers shared a common feature: displacement of the modified guanine from the double helix. In the global minimum, the aminopyrene residue was inserted in the helix in the site of displaced guanine. In other low energy structures, the aminopyrene was also displaced towards the minor groove (in addition to guanine), or partly inserted and partly in the groove. More conventional structures were also encountered, with anti-guanine within the helix and aminopyrene in the major groove, or syn-guanine within the helix, and aminopyrene in the minor groove. Such structures were 12-20 kcal/mol less stable than the global minimum, however. The C8-guanine adduct of aminopyrene thus appears to perturb the B-DNA structure to a greater extent than do the adducts of less bulky amines such as aminofluorene and 4-aminobiphenyl.