Conformational perturbation of the anticancer nucleotide arabinosylcytosine on Z-DNA: molecular structure of (araC-dG)3 at 1.3 A resolution.

The left-handed Z-DNA structure of an araC-containing (where araC stands for arabinosylcytosine) hexamer, (araC-dG)3, has been solved by x-ray diffraction analysis at 1.3 A resolution. This hexamer was crystallized in the hexagonal P6(5)22 (a = b = 17.96 A, c = 43.22 A) space group in which the hexamers have statistically disordered packing arrangement along the 6(5) screw axis, yet the crystals diffract x-rays to high resolution. Its structure has been refined by the constrained least square refinement to a final R factor of 0.287 using 737 [> 3.0 sigma(F)] observed reflections. The asymmetric unit of the unit cell contains only a dinucleotide, 5'-p (araC)p(dG). The overall conformation resembles that of the canonical Z-DNA, but with some differences in details. The O2' hydroxyl groups of the araC residues form intramolecular hydrogen bonds with N2 of the 5'-guanine residues. In the deep groove of Z-DNA, these hydroxy groups replace the bridging water molecules that stabilize the guanine in the syn conformation. The results reinforce the earlier observation made by the structural analysis of another hexamer, d(CG[araC]GCG), with a mono-substitution of araC [M.-K. Teng, Y.-C. Liaw, G. A. van der Marel, J. H. van Boom, and A. H.-J. Wang (1989) Biochemistry, vol. 28, pp. 4923-4928]. These two structures show that araC residue can be incorporated readily into the Z structure and probably facilitates the B to Z transition, as supported by uv absorption spectroscopic studies in a number of araC-containing oligonucleotides. The potential biological roles of the araC-modified Z-DNA are discussed.     

Structure of a B-DNA decamer with a central T-A step: C-G-A-T-T-A-A-T-C-G.

The X-ray crystal structure analysis of the decamer C-G-A-T-T-A-A-T-C-G has been carried out to a resolution of 1.5 A. The crystals are space group P2(1)2(1)2(1), cell dimensions a = 38.60 A, b = 39.10 A, c = 33.07 A. The structure was solved by molecular replacement and refined with X-PLOR and NUCLSQ. The final R factor for a model with 404 DNA atoms, 108 water molecules and one magnesium hexahydrate cation is 15.7%. The double helix is essentially isostructural with C-G-A-T-C-G-A-T-C-G, with closely similar local helix parameters. The structure of the T-T-A-A center differs from that found in C-G-C-G-T-T-A-A-C-G-C-G in that the minor groove in our decamer is wide at the central T-A step rather than narrow, and the twist angle of the T-A step is small (31.1 degrees) rather than large. Whereas the tetrad model provides a convenient framework for discussing local DNA helix structure, it cannot be the entire story. The articulated helix model of DNA structure proposes that certain sequence regions of DNA show preferential twisting or bending properties, whereas other regions are less capable of deformation, in a manner that may be useful in sequence recognition by drugs and protein. Further crystal structure analyses should help to delineate the precise nature of sequence-dependent articulation in the DNA double helix.     

A novel end-to-end binding of two netropsins to the DNA decamers d(CCCCCIIIII)2, d(CCCBr5CCIIIII)2and d(CBr5CCCCIIIII)2.

Netropsin is bound to the DNA decamer d(CCCCCIIIII)2, the C-4 bromo derivative d(CCCBr5CCIIIII)2and the C-2 bromo derivative d(CBr5CCCCIIIII)2in a novel 2:1 mode. Complexes of the native decamer and the C-4 bromo derivative are isomorphous, space group P1, unit cell dimensions a = 32.56 A (32.66), b = 32.59 A (32.77), c = 37.64 A (37.71), alpha = 86.30 degrees (86.01 degrees), beta = 84.50 degrees (84.37 degrees), gamma = 68.58 degrees (68.90 degrees) with two independent molecules (A and B) in the asymmetric unit (values in parentheses are for the derivative). The C-2 bromo derivative is hexagonal P61, unit cell dimensions a = b = 32.13 A, c = 143.92, gamma = 120 degrees with one molecule in the asymmetric unit. The structures were solved by the molecular replacement method. The novelty of the structures is that there are two netropsins bound end-to-end in the minor groove of each B-DNA decamer which has nearly a complete turn. The netropsins are held by hydrogen bonding interactions to the base atoms and by sandwiching van der Waal's interactions from the sugar-phosphate backbones of the double helix similar to every other drug.DNA complex. Each netropsin molecule spans approximately 5 bp. The netropsins refined with their guanidinium heads facing each other at the center, although an orientational disorder for the netropsins cannot be excluded. The amidinium ends stretch out toward the junctions and bind to the adjacent duplexes in the columns of stacked symmetry-related complexes. Both cationic ends of netropsin are bridged by water molecules in one of the independent molecules (molecule A) of the triclinic structures and also the hexagonal structure to form pseudo-continuous drug.decamer helices.     

Molecular structure of an A-DNA decamer d(ACCGGCCGGT)

The molecular structure of the DNA decamer d(ACCGGCCGGT) has been solved and refined by single-crystal X-ray-diffraction analysis at 0.20 nm to a final R-factor of 18.0%. The decamer crystallizes as an A-DNA double helical fragment with unit-cell dimensions of a = b = 3.923 nm and c = 7.80 nm in the space group P6(1)22. The overall conformation of this A-DNA decamer is very similar to that of the fiber model for A-DNA which has a large average base-pair tilt and hence a wide and shallow minor groove. This structure is in contrast to that of several A-DNA octamers in which the molecules all have low base-pair-tilt angles (8-12 degrees) resulting in an appearance intermediate between B-DNA and A-DNA. The average helical parameters of this decamer are typical of A-DNA with 10.9 base pairs/turn of helix, an average helical twist angle of 33.1 degrees, and a base-pair-tilt angle of 18.2 degrees. However, the CpG step in this molecule has a low local-twist angle of 24.5 degrees, similar to that seen in other A-DNA oligomers, and therefore appears to be an intrinsic stacking pattern for this step. The molecules pack in the crystal using a recurring binding motif, namely, the terminal base pair of one helix abuts the surface of the shallow minor groove of another helix. In addition, the GC base pairs have large propeller-twist angles, unlike those found most other A-DNA structures.     

Crystallographic study of one turn of G/C-rich B-DNA

The DNA decamer d(CCAGGCCTGG) has been studied by X-ray crystallography. At a nominal resolution of 1.6 A, the structure was refined to R = 16.9% using stereochemical restraints. The oligodeoxyribonucleotide forms a straight B-DNA double helix with crystallographic dyad symmetry and ten base-pairs per turn. In the crystal lattice, DNA fragments stack end-to-end along the c-axis to form continuous double helices. The overall helical structure and, notably, the groove dimensions of the decamer are more similar to standard, fiber diffraction-determined B-DNA than A-tract DNA. A unique stacking geometry is observed at the CA/TG base-pair step, where an increased rotation about the helix axis and a sliding motion of the base-pairs along their long axes leads to a superposition of the base rings with neighboring carbonyl and amino functions. Three-center (bifurcated) hydrogen bonds are possible at the CC/GG base-pair steps of the decamer. In their common sequence elements, d(CCAGGCCTGG) and the related G.A mismatch decamer d(CCAAGATTGG) show very similar three-dimensional structures, except that d(CCAGGCCTGG) appears to have a less regularly hydrated minor groove. The paucity of minor groove hydration in the center of the decamer may be a general feature of G/C-rich DNA and explain its relative instability in the B-form of DNA.     

Structure of the B-DNA decamer C-C-A-A-C-G-T-T-G-G and comparison with isomorphous decamers C-C-A-A-G-A-T-T-G-G and C-C-A-G-G-C-C-T-G-G

The crystal structure of the DNA decamer C-C-A-A-C-G-T-T-G-G has been solved to a resolution of 1.4 A, and is compared with the 1.3 A structure of C-C-A-A-G-A-T-T-G-G and the 1.6 A structure of C-C-A-G-G-C-C-T-G-G. All three decamers crystallize isomorphously in space group C2 with five base-pairs per asymmetric unit, and with decamer double helices stacked atop one another along the c axis in a manner that closely approximates a continuous B helix. This efficient stacking probably accounts for the high resolution of the crystal data. Comparison of the three decamers reveals the following. (1) Minor groove width is more variable than heretofore realized. Regions of A.T base-pairs tend to be narrower than average, although two successive A.T base-pairs alone may not be sufficient to produce narrowing. The minor groove is wider in regions where BII phosphate conformations are opposed diagonally across the groove. (2) Narrow regions of minor groove exhibit a zig-zag spine of hydration, as was first seen in C-G-C-G-A-A-T-T-C-G-C-G, whereas wide regions show two ribbons of water molecules down the walls, connecting base edge N or O with sugar O-4' atoms. Regions of intermediate groove width may accommodate neither pattern of hydration well, and may exhibit a less regular pattern of hydration. (3) Base-pair stacking is virtually identical at equivalent positions in the three decamers. The unconnected step from the top of one decamer helix to the bottom of the next helix is a normal helix step in all respects, except for the absence of connecting phosphate groups. (4) BII phosphate conformation require the unstacking of the two bases linked by the phosphate, but do not necessarily follow as an inevitable consequence of unstacking. They have an influence on minor groove width as noted in point (1) above. (5) Sugar ring pseudorotation P and main-chain torsion angle delta show an excellent correlation as given by the equation: delta = 40 degrees cos (P + 144 degrees) + 120 degrees. Although centered around C-2'-endo, the conformations in these B-DNA helices are distributed broadly from C-3'-exo to O-4'-endo, unlike the tighter clustering around C-3'-endo observed in A-DNA oligomer structures.     

Selective inhibition by arabinosylcytosine of oligo(U)-containing RNA synthesis in germinating wheat embryos

Arabinosylcytosine (araC) was found to influence the pattern of RNA labelling in early wheat embryos. Although the rate of uridine-¹⁴C incorporation into total RNA remained unchanged, specific radioactivity of an oligo(U)-containing subclass of nonpolyadenylated RNA was markedly lower (50%) in araC-treated (1.5 mM, 1 h) than in control embryos. The inhibitory effect was stronger for nuclear than for cytoplasmic subpopulation of these RNA species. h labelling of all other RNA fractions, including bulk nonpolyadenylated RNA as well as poly(A)-containing RNA of both nuclear and cytoplasmic origins, did not respond to the presence of araC.     

Mutations in the araC regulatory gene of Escherichia coli B/r that affect repressor and activator functions of AraC protein.

Mutations in the araC gene of Escherichia coli B/r were isolated which alter both activation of the araBAD operon expression and autoregulation. The mutations were isolated on an araC-containing plasmid by hydroxylamine mutagenesis of plasmid DNA. The mutant phenotype selected was the inability to autoregulate. The DNA sequence of 16 mutants was determined and found to consist of seven different missense mutations located within the distal third of the araC gene. Enzyme activities revealed that each araC mutation had altered both autoregulatory and activator functions of AraC protein. The mutational analysis presented in this paper suggests that both autoregulatory and activator functions are localized to the same determinants of the AraC protein and that the amino acid sequence within the carboxy-terminal region of AraC protein is important for site-specific DNA binding.     

Phased psoralen cross-links do not bend the DNA double helix

Although the chemical reaction of psoralens with nucleic acids is well understood, the structure of psoralen-DNA cross-linked products is still not clear. Model building studies base on the crystal structure of the psoralen-thymine monoadduct suggest that each cross-link bends the DNA double helix by 46.5 degrees [Pearlman, D. A., Holbrook, S. R., Pirkle, D. H., & Kim, S.-H. (1985) Science (Washington, D.C.) 227, 1304-1308]. On the other hand, Sinden and Hagerman [Sinden, R. R., & Hagerman, P. J. (1984) Biochemistry 23, 6299-6303] find that, in solution, psoralen cross-linked DNA is not bent. Here we use gel electrophoresis to test the validity of the current models. We have synthesized a series of DNA fragments (21-24 base pairs in length), each containing one unique T-A site for 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) cross-linking. Because of an estimated 28 degrees unwinding of the helix by HMT [Wiesehahn, G., & Hearst, J. E. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 2703-2707], one expects that the 22-bp cross-linked fragment will be repeated nearly in phase with the average helical screw when multimerized. In that sequence ligation will maximally amplify any deformation to the double helix. We find that the ligated multimers of cross-linked DNA migrate close to the multimers of non-cross-linked DNA on polyacrylamide gels. Our observations place an upper limit of 10 degrees on DNA bending induced by psoralen cross-linking and indicate unwinding by about 1 bp, as well as stiffening of the double helix. These properties are not unexpected for classical intercalators.     

Effects of the O2' hydroxyl group on Z-DNA conformation: structure of Z-RNA and (araC)-[Z-DNA

The left-handed Z structures of two hexamers [d(CG)r(CG)d(CG) and d(CG)(araC)d(GCG)] containing ribose and arabinose residues have been solved by X-ray diffraction analysis at 1.5-A resolution. Their conformations closely resemble that of the canonical Z-DNA. The O2' hydroxyl groups of both rC and araC residues form intramolecular hydrogen bonds with N2 of the 5' guanine residue and replace the bridging water molecules in the deep groove of Z-DNA, which stabilize the guanine in the syn conformation. The araC residue can be incorporated into the Z structure readily and facilitates B to Z transition, as supported by UV absorption spectroscopic studies. In contrast, in Z-RNA the ribose of the cytidine residue is twisted in order to form the respective hydrogen bond. The potential biological roles of the modified Z-DNA containing anticancer nucleoside araC and of Z-RNA are discussed.     

The crystal structure of EcoRV endonuclease and of its complexes with cognate and non-cognate DNA fragments.

The crystal structure of EcoRV endonuclease has been determined at 2.5 A resolution and that of its complexes with the cognate DNA decamer GGGATATCCC (recognition sequence underlined) and the non-cognate DNA octamer CGAGCTCG at 3.0 A resolution. Two octamer duplexes of the non-cognate DNA, stacked end-to-end, are bound to the dimeric enzyme in B-DNA-like conformations. The protein--DNA interactions of this complex are prototypic for non-specific DNA binding. In contrast, only one cognate decamer duplex is bound and deviates considerably from canonical B-form DNA. Most notably, a kink of approximately 50 degrees is observed at the central TA step with a concomitant compression of the major groove. Base-specific hydrogen bonds between the enzyme and the recognition base pairs occur exclusively in the major groove. These interactions appear highly co-operative as they are all made through one short surface loop comprising residues 182-186. Numerous contacts with the sugar phosphate backbone extending beyond the recognition sequence are observed in both types of complex. However, the total surface area buried on complex formation is > 1800 A2 larger in the case of cognate DNA binding. Two acidic side chains, Asp74 and Asp90, are close to the reactive phosphodiester group in the cognate complex and most probably provide oxygen ligands for binding the essential cofactor Mg2+. An important role is also indicated for Lys92, which together with the two acidic functions appears to be conserved in the otherwise unrelated structure of EcoRI endonuclease. The structural results give new insight into the physical basis of the remarkable sequence specificity of this enzyme.     

Crystal structure of the topoisomerase II poison 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide bound to the DNA hexanucleotide d(CGTACG)2.

The structure of the complex formed between d(CGTACG)(2) and the antitumor agent 9-amino-[N-(2-dimethylamino)ethyl]acridine-4-carboxamide has been solved to a resolution of 1.6 A using X-ray crystallography. The complex crystallized in space group P6(4) with unit cell dimensions a = b = 30.2 A and c = 39.7 A, alpha = beta = 90 degrees, gamma = 120 degrees. The asymmetric unit contains a single strand of DNA, 1. 5 drug molecules, and 29 water molecules. The final structure has an overall R factor of 19.3%. A drug molecule intercalates between each of the CpG dinucleotide steps with its side chain lying in the major groove, and the protonated dimethylamino group partially occupies positions close to ( approximately 3.0 A) the N7 and O6 atoms of guanine G2. A water molecule forms bridging hydrogen bonds between the 4-carboxamide NH and the phosphate group of the same guanine. Sugar rings adopt the C2'-endo conformation except for cytosine C1 which moves to C3'-endo, thereby preventing steric collision between its C2' methylene group and the intercalated acridine ring. The intercalation cavity is opened by rotations of the main chain torsion angles alpha and gamma at guanines G2 and G6. Intercalation perturbs helix winding throughout the hexanucleotide compared to B-DNA, steps 1 and 2 being unwound by 8 degrees and 12 degrees, respectively, whereas the central TpA step is overwound by 17 degrees. An additional drug molecule, lying with the 2-fold axis in the plane of the acridine ring, is located at the end of each DNA helix, linking it to the next duplex to form a continuously stacked structure. The protonated N,N-dimethylamino group of this "end-stacked" drug hydrogen bonds to the N7 atom of guanine G6. In both drug molecules, the 4-carboxamide group is internally hydrogen bonded to the protonated N-10 atom of the acridine ring. The structure of the intercalated complex enables a rationalization of the known structure-activity relationships for inhibition of topoisomerase II activity, cytotoxicity, and DNA-binding kinetics for 9-aminoacridine-4-carboxamides.     

Unusual DNA conformation at low pH revealed by NMR: parallel-stranded DNA duplex with homo base pairs.

We have investigated the conformational potentials of several DNA oligonucleotides containing sequences related to 5'-CGA in neutral pH and low pH (< 5.0) conditions. One-dimensional proton NMR spectra show that d(CGATCG), d(TCGATCGA), and d(CGATCGATCG) exhibit new sets of resonances at low pH (approximately 3.8-4.4), when compared to those from the neutral pH samples. The low pH form and the neutral pH form are in slow equilibrium. Analyses of the data suggest that these sequences under low pH conditions adopt structures distinct from B-DNA. Two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY) data from the DNA hexamer d(CGATCG) of the neutral and low pH samples were used to analyze their respective structures in solution. An iterative NOE spectral-driven refinement procedure, SPEDREF [Robinson, H., & Wang, A. H.-J. (1992) Biochemistry 31, 3524-3533], was used to show that the neutral pH structure is close to canonical B-DNA. In contrast, analysis of the low pH form using the 2D NOESY data suggests that its structure is consistent with a right-handed parallel-stranded (PS) double helix with symmetrical non-Watson-Crick (C+:C, G:G, A:A, T:T) homo base pairs. Supporting evidence for the PS helix includes the asymmetric inversion-recovery relaxation times associated with the two ends of the helix. The structure is favored by the 5'-CGA sequence in which the cytosines provide the C+:C pairing for the nucleation step and the GpA step is significantly stabilized by the interstrand G-A stacking interactions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of counter-ions on the crystal structures of DNA decamers: binding of [Co(NH3)6]3+ and Ba2+ to A-DNA.

A-DNA is a stable alternative right-handed double helix that is favored by certain sequences (e.g., (dG)n.(dC)n) or under low humidity conditions. Earlier A-DNA structures of several DNA oligonucleotides and RNA.DNA chimeras have revealed some conformational variation that may be the result of sequence-dependent effects or crystal packing forces. In this study, four crystal structures of three decamer oligonucleotides, d(ACCGGCCGGT), d(ACCCGCGGGT), and r(GC)d(GTATACGC) in two crystal forms (either the P6(1)22 or the P2(1)2(1)2(1) space group) have been analyzed at high resolution to provide the molecular basis of the structural difference in an experimentally consistent manner. The study reveals that molecules crystallized in the same space group have a more similar A-DNA conformation, whereas the same molecule crystallized in different space groups has different (local) conformations. This suggests that even though the local structure is influenced by the crystal packing environments, the DNA molecule adjusts to adopt an overall conformation close to canonical A-DNA. For example, the six independent CpG steps in these four structures have different base-base stacking patterns, with their helical twist angles (omega) ranging from 28 degrees to 37 degrees. Our study further reveals the structural impact of different counter-ions on the A-DNA conformers. [Co(NH3)6]3+ has three unique A-DNA binding modes. One binds at the major groove side of a GpG step at the O6/N7 sites of guanine bases via hydrogen bonds. The other two modes involve the binding of ions to phosphates, either bridging across the narrow major groove or binding between two intra-strand adjacent phosphates. Those interactions may explain the recent spectroscopic and NMR observations that [Co(NH3)6]3+ is effective in inducing the B- to A-DNA transition for DNA with (G)n sequence. Interestingly, Ba2+ binds to the same O6/N7 sites on guanine by direct coordinations.     

The conformation of a B-DNA decamer is mainly determined by its sequence and not by crystal environment.

By comparing the conformations adopted by a double-stranded decameric B-DNA fragment in different crystal environments, we address the question of the degree of deformability of DNA helices. The three-dimensional structure of the self-complementary DNA decamer CCAGGCmeCTGG has been determined from crystals of space group P6 at 2.25 A resolution with an R value of 17.2% for 2407 1 sigma structure amplitudes. The oligonucleotide forms a B-type double helix with a characteristic sequence-dependent conformation closely resembling that of the corresponding unmethylated decamer, the structure of which is known from a high-resolution analysis of crystals of space group C2. Evidently, both the effects of single-site methylation and altered crystal environment on the DNA conformation are small. Therefore, double-helical DNA may possess sequence-determined conformational features that are less deformable than previously thought.     

Interaction between a DNA oligonucleotide and a dinuclear iron(II) supramolecular cylinder; an NMR and molecular dynamics study

A tetracationic supramolecular cylinder, [Fe(2)L(3)](4+) (L=C(25)H(20)N(4)), with a triple-helical architecture, is just the right size to fit into the major groove of DNA but too big to fit into the minor groove. A detailed NMR spectroscopic analysis supported by molecular dynamics (MD) calculations shows unambiguously the close fit between the cylinder and a duplex oligonucleotide, [d(GACGGCCGTC)(2)]. Furthermore, only the left-handed enantiomer of the cylinder seems to fit the groove geometry. With both free and complexed species of [Fe(2)L(3)](4+) and DNA in solution, the NMR spectra are too complicated for a detailed structure determination. Based on differences in chemical shifts and extensive MD calculations, a realistic qualitative picture of the DNA-cylinder adduct is presented. Several sets of chemical shifts assigned to the protons of the three ligand strands in the cylinder indicate that the iron complex situated in the major groove exhibits restricted rotation on the NMR timescale around the cylindrical axis. The NMR NOE data support a model where the cylinder undergoes both a translational and rotational oscillation in the major groove. The results of an NOE restrained MD calculation indicates that the cylinder induces a 40 degrees bend of the double helix, in accordance with linear dichroism measurements. Other distinct features to be noticed are the very low value of the helical twist (16 degrees) induced at the G(4)C(5) step.     

Crystal structure of the self-complementary 5''-purine start decamer d(GCACGCGTGC) in the A-DNA conformation. II.

The crystal structure of the alternating 5'-purine start decamer d(GCGCGCGCGC) was found to be in the left-handed Z-DNA conformation. Inasmuch as the A.T base pair is known to resist Z-DNA formation, we substituted A.T base pairs in the dyad-related positions of the decamer duplex. The alternating self-complementary decamer d(GCACGCGTGC) crystallizes in a different hexagonal space group, P6(1)22, with very different unit cell dimensions a = b = 38.97 and c = 77.34 A compared with the all-G.C alternating decamer. The A.T-containing decamer has one strand in the asymmetric unit, and because it is isomorphous to some other A-DNA decamers it was considered also to be right-handed. The structure was refined, starting with the atomic coordinates of the A-DNA decamer d(GCGGGCCCGC), by use of 2491 unique reflections out to 1.9-A resolution. The refinement converged to an R value of 18.6% for a total of 202 nucleotide atoms and 32 water molecules. This research further demonstrates that A.T base pairs not only resist the formation of Z-DNA but can also assist the formation of A-DNA by switching the helix handedness when the oligomer starts with a 5'-purine; also, the length of the inner Z-DNA stretch (d(CG)n) is reduced from an octamer to a tetramer. It may be noted that these oligonucleotide properties are in crystals and not necessarily in solutions.     

Structure of poly 8-bromoadenylic acid; conformational studies by CPF energy calculations.

Poly 8-bromoadenylic acid [poly(BBrA)] is the only known all-syn polynucleotide. It shows a helix-coil transition with a melting curve centred around 55 degrees C. Energy calculations based on classical potential functions have been used to explore the three-dimensional structure of this polymer in helix and random coil. It is concluded that the ordered state is a helix of two parallel strands with a two-fold rotation axis, and the duplex is stabilised by hydrogen bonds involving N1 and H6. Each strand has a conformation with C3' endo geometry, phi' = 216 degrees, omega' = 280 degrees, omega = 294 degrees, phi = 179 degrees, chi = 243 degrees and psi = 57 degrees. Such a conformation leads to approximately 8 nucleotide units per turn of the helix and an axial rise of 3.9A degrees. The structure of poly(8BrA) has been compared with that of the related polymer poly(A) which forms a double helical structure in acidic conditions with bases in the anti conformation and with interstrand hydrogen-bonds between N7 and H6. This is the first time that a specific geometrical model of a novel polynucleotide structure has been produced initially by potential energy calculations, though such calculations on a number of known structures have been reported previously.