Molecular Dynamics Simulation of a PNA·DNA·PNA Triple Helix in Aqueous Solution

Molecular dynamics simulations have been used to explore the conformational flexibility of a PNA·DNA·PNA triple helix in aqueous solution. Three 1.05 ns trajectories starting from different but reasonable conformations have been generated and analyzed in detail. All three trajectories converge within about 300 ps to produce stable and very similar conformational ensembles, which resemble the crystal structure conformation in many details. However, in contrast to the crystal structure, there is a tendency for the direct hydrogen-bonds observed between the amide hydrogens of the Hoogsteen-binding PNA strand and the phosphate oxygens of the DNA strand to be replaced by water-mediated hydrogen bonds, which also involve pyrimidine O2 atoms. This structural transition does not appear to weaken the triplex structure but alters groove widths and so may relate to the potential for recognition of such structures by other ligands (small molecules or proteins). Energetic analysis leads us to conclude that the reason that the hybrid PNA/DNA triplex has quite different helical characteristics from the all-DNA triplex is not because the additional flexibility imparted by the replacement of sugar−phosphate by PNA backbones allows motions to improve base-stacking but rather that base-stacking interactions are very similar in both types of triplex and the driving force comes from weak but definate conformational preferences of the PNA strands.

Molecular Dynamics Simulations of the d(TAT) Triple Helix

Molecular dynamics (MD) simulations have been used to study the dynamical and time-averaged characteristics of the DNA triple helix d(T)10âd(A)10âd(T)10. The structures sampled during the trajectory resemble closely the B-type model for the DNA triplex proposed on the basis of NMR data, although there are some subtle differences. Alternative P- and A-type conformations for the triplex, suggested from X-ray experiments, are not predicted to contribute significantly to the structure of the DNA triplex in solution. Comparison with the best available experimental data supports the correctnes of the MD-generated structures. The analysis of the collected data gives a detailed picture of the characteristics of triple-helix DNA. A new and interesting pattern of hydration, specific for triplex DNA, is an important observation. The results suggest that molecular dynamics can be useful for the study of novel nucleic acid structures.

Decompression during Late Proterozoic Al2SiO5 Triple-Point Metamorphism at Cerro Colorado, New Mexico

An outstanding problem in understanding the late Proterozoic tectonic assembly of the southwest is identifying the tectonic setting associated with regional metamorphism at 1.4 Ga. Both isobaric heating and cooling, and counter-clockwise looping PT paths are proposed for this time. We present a study of the Proterozoic metamorphic and deformation history of the Cerro Colorado area, southern Tusas Mountains, New Mexico, which shows that the metamorphism in this area records near-isothermal decompression from 6 to 4 kbar at ca. 1.4 Ga. We do not see evidence for isobaric heating at this time. Decompression from peak pressures is recorded by the reaction Ms + Grt = St + Bt, with a negative slope in PT space; the reaction Ms + Grt = Sil + Bt, which is nearly horizontal in PT space; and partial to total pseudomorphing of kyanite by sillimanite during the main phase of deformation. The clearest reaction texture indicating decompression near peak metamorphic temperature is the replacement of garnet by clots of sillimanite, which are surrounded by halos of biotite. The sillimanite clots, most without relict garnet in the cores and with highly variable aspect ratios, are aligned. They define a lineation that formed with the dominant foliation. An inverted metamorphic gradient is locally defined by sillimanite-garnet schists (625 degrees C) structurally above staurolite-garnet schists (550 degrees C) and implies ductile thrusting during the main phase of deformation. The exhumation that led to the recorded decompression was likely in response to crustal thickening due to ductile thrusting and subsequent denudation.

Femtosecond Rotational Raman Coherence Spectroscopy of Cyclohexane in a Pulsed Supersonic Jet

We combine the technique of femtosecond degenerate four-wave mixing (fs-DFWM) with a high repetition-rate pulsed supersonic jet source to obtain the rotational coherence spectrum (RCS) of cold cyclohexane (C(6)H(12)) with high signal/noise ratio. In the jet expansion, the near-parallel flow pattern combined with rapid translational cooling effectively eliminate dephasing collisions, giving near-constant RCS signal intensities over time delays up to 5 ns. The vibrational cooling in the jet eliminates the thermally populated vibrations that complicate the RCS coherences of cyclohexane at room temperature [Bragger, G.; et al. J. Phys. Chem. A 2011, 115, 9567]. The rotational cooling reduces the high-J rotational-state population, yielding the most accurate ground-state rotational constant to date, B(0) = 4305.859(9) MHz. Based on this B(0), a reanalysis of previous room-temperature gas-cell RCS measurements of cydohexane gives improved vibration rotation interaction constants for the v(32), v(6), v(16), and v(24) vibrational states. Combining the experimental B(0)(C(6)H(12)) with CCSD(T) calculations yields a very accurate semiexperimental equilibrium structure of the chair isomer of cyclohexane

N-H center dot center dot center dot pi hydrogen-bonding and large-amplitude tipping vibrations in jet-cooled pyrrole-benzene

The N-H center dot center dot center dot pi hydrogen bond is an important intermolecular interaction in many biological systems. We have investigated the infrared (IR) and ultraviolet (UV) spectra of the supersonic-jet cooled complex of pyrrole with benzene and benzene-d(6) (Pyr center dot Bz, Pyr center dot Bz-d(6)). DFT-D density functional, SCS-MP2 and SCS-CC2 calculations predict a T-shaped and (almost) C(s) symmetric structure with an N-H center dot center dot center dot pi hydrogen bond to the benzene ring. The pyrrole is tipped by omega(S(0)) = +/- 13 degrees relative to the surface normal of Bz. The N center dot center dot center dot ring distance is 3.13 angstrom. In the S(1) excited state, SCS-CC2 calculations predict an increased tipping angle omega(S(1)) = +/- 21 degrees. The IR depletion spectra support the T-shaped geometry: The NH stretch is redshifted by -59 cm(-1), relative to the "free" NH stretch of pyrrole at 3531 cm(-1), indicating a moderately strong N-H center dot center dot center dot pi interaction. The interaction is weaker than in the (Pyr)(2) dimer, where the NH donor shift is -87 cm(-1) [Dauster et al., Phys. Chem. Chem. Phys., 2008, 10, 2827]. The IR C-H stretch frequencies and intensities of the Bz subunit are very similar to those of the acceptor in the (Bz)(2) dimer, confirming that Bz acts as the acceptor. While the S(1) <- S(0) electronic origin of Bz is forbidden and is not observable in the gas-phase, the UV spectrum of Pyr center dot Bz in the same region exhibits a weak 0(0)(0) band that is red-shifted by 58 cm(-1) relative to that of Bz (38 086 cm(-1)). The origin appears due to symmetry-breaking of the p-electron system of Bz by the asymmetric pyrrole NH center dot center dot center dot pi hydrogen bond. This contrasts with (Bz)(2), which does not exhibit a 0(0)(0) band. The Bz moiety in Pyr center dot Bz exhibits a 6a(0)(1) band at 0(0)(0) + 518 cm(-1) that is about 20x more intense than the origin band. The symmetry breaking by the NH center dot center dot center dot pi hydrogen bond splits the degeneracy of the v(6)(e(2g)) vibration, giving rise to 6a' and 6b' sub-bands that are spaced by similar to 6 cm(-1). Both the 0(0)(0) and 6(0)(1) bands of Pyr center dot Bz carry a progression in the low-frequency (10 cm(-1)) excited-state tipping vibration omega', in agreement with the change of the omega tipping angle predicted by SCS-MP2 and SCS-CC2 calculations.

Vibronic Spectra of Jet-Cooled 2-Aminopurine center dot H2O Clusters Studied by UV Resonant Two-Photon Ionization Spectroscopy and Quantum Chemical Calculations

For understanding the major- and minor-groove hydration patterns of DNAs and RNAs, it is important to understand the local solvation of individual nucleobases at the molecular level. We have investigated the 2-aminopurine center dot H2O. monohydrate by two-color resonant two-photon ionization and UV/UV hole-burning spectroscopies, which reveal two isomers, denoted A and B. The electronic spectral shift delta nu of the S-1 <- S-0 transition relative to bare 9H-2-aminopurine (9H-2AP) is small for isomer A (-70 cm(-1)), while that of isomer B is much larger (delta nu = 889 cm(-1)). B3LYP geometry optimizations with the TZVP basis set predict four cluster isomers, of which three are doubly H-bonded, with H2O acting as an acceptor to a N-H or -NH2 group and as a donor to either of the pyrimidine N sites. The "sugar-edge" isomer A is calculated to be the most stable form with binding energy D-e = 56.4 kJ/mol. Isomers B and C are H-bonded between the -NH2 group and pyrimidine moieties and are 2.5 and 6.9 kJ/mol less stable, respectively. Time-dependent (TD) B3LYP/TZVP calculations predict the adiabatic energies of the lowest (1)pi pi* states of A and B in excellent agreement with the observed 0(0)(0) bands; also, the relative intensities of the A and B origin bands agree well with the calculated S-0 state relative energies. This allows unequivocal identification of the isomers. The R2PI spectra of 9H-2AP and of isomer A exhibit intense low-frequency out-of-plane overtone and combination bands, which is interpreted as a coupling of the optically excited (1)pi pi* state to the lower-lying (1)n pi* dark state. In contrast, these overtone and combination bands are much weaker for isomer B, implying that the (1)pi pi* state of B is planar and decoupled from the (1)n pi* state. These observations agree with the calculations, which predict the (1)n pi* above the (1)pi pi* state for isomer B but below the (1)pi pi* for both 9H-2AP and isomer A.