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V T Forsyth

Publications and source records attributed to V T Forsyth.

12 recordsLinked to original sources
PubMed2006

Phonon dispersion of oriented DNA by inelastic x-ray scattering.

Films of oriented deoxyribonucleic acid (DNA), prepared by the wet spinning method, have been studied using inelastic x-ray scattering. Spectra were recorded within the range of energy transfers -30< homega <30 meV at momentum transfers homegaQ ranging from 2.5 to 30 nm(-1) whereby the direction of Q essentially coincided with the helical axis. Measurements at ambient temperature cover samples in the A, B, C, and D conformations of DNA. Within the limits of the instrumental resolution, the spectra were analyzed by the response of a damped harmonic oscillator delivering dispersion and damping of modes having displacements with nonzero projections onto Q, i.e., essentially the compression waves traveling along the helical axis. The longitudinal speed of sound resulting from the sinusoidal dispersion varies only weakly with conformation. Our sound speed values are compared to results from Brillouin spectroscopy. The dispersion curves exhibit a minimum at about the inverse rise per residue, which -- together with strong elastic scattering -- reflect the large degree of disorder. Overdamping of the modes is observed for Q>5 nm(-1). The possibility that the observed large damping parameters are due to several contributing modes is discussed in terms of a simple model calculation for an idealized double helix. Whereas the quasicrystalline approximation for an effective disordered chain could well describe the sinusoidal dispersion, it fails to reproduce the observed damping by one order of magnitude. Our results indicate that the high-frequency dynamics of DNA is liquidlike and is most appropriately described by instantaneous normal modes of short correlation length.

DNA↗
PubMed2005

Neutron vibrational spectroscopy gives new insights into the structure of poly(p-phenylene terephthalamide).

The vibrational spectra of benzanilide and poly(p-phenylene terephthalamide) have been measured using inelastic neutron scattering. These compounds have similar hydrogen-bond networks, which, for poly(p-phenylene terephthalamide), lead to two-dimensional hydrogen-bonded sheets in the crystal. Experimental spectra are compared with solid-state, quantum chemical calculations based on density functional theory (DFT). Such "parameter-free" calculations allow the structure-dynamics relation in this type of compound to be quantified, which is demonstrated here for benzanilide. In the case of poly(p-phenylene terephthalamide), vibrational spectroscopy and DFT calculations help resolve long-standing questions about the packing of hydrogen-bonded sheets in the solid state.

Journal Article↗
PubMed2000

A peptide from the adenovirus fiber shaft forms amyloid-type fibrils.

The fiber protein of adenovirus consists of a C-terminal globular head, a shaft and a short N-terminal tail. The crystal structure of a stable domain comprising the head plus a part of the shaft of human adenovirus type 2 fiber has recently been solved at 2.4 A resolution [van Raaij et al. (1999) Nature 401, 935-938]. A peptide corresponding to the portion of the shaft immediately adjacent to the head (residues 355-396) has been synthesized chemically. The peptide failed to assemble correctly and instead formed amyloid-type fibrils as assessed by electron microscopy, Congo red binding and X-ray diffraction. Peptides corresponding to the fiber shaft could provide a model system to study mechanisms of amyloid fibril formation.

Adenoviruses, Human↗
PubMed1996

DNA hydration studied by neutron fiber diffraction.

The development of neutron high angle fiber diffraction to investigate the location of water around the deoxyribonucleic acid (DNA) double-helix is described. The power of the technique is illustrated by its application to the D and A conformations of DNA using the single crystal diffractometer, D19, at the Institut Laue-Langevin. Grenoble and the time of flight diffractometer, SXD, at the Rutherford Appleton ISIS Spallation Neutron Source. These studies show the existence of bound water closely associated with the DNA. The patterns of hydration in these two DNA conformations are quite distinct and are compared to those observed in X-ray single crystal studies of two-stranded oligodeoxynucleotides. Information on the location of water around the DNA double-helix from the neutron fiber diffraction studies is combined with that on the location of alkali metal cations from complementary X-ray high angle fiber diffraction studies at the Daresbury Laboratory SRS using synchrotron radiation. These analyses emphasize the importance of viewing DNA, water and ions as a single system with specific interactions between the three components and provide a basis for understanding the effect of changes in the concentration of water and ions in inducing conformational transitions in the DNA double-helix.

Crystallography↗
PubMed1996

Time-of-flight Laue fiber diffraction studies of perdeuterated DNA.

The diffractometer SXD at the Rutherford Appleton Laboratory ISIS pulsed neutron source has been used to record high resolution time-of-flight Laue fiber diffraction data from DNA. These experiments, which are the first of their kind, were undertaken using fibers of DNA in the A conformation and prepared using deuterated DNA in order to minimise incoherent background scattering. These studies complement previous experiments on instrument D19 at the Institut Laue Langevin using monochromatic neutrons. Sample preparation involved drawing large numbers of these deuterated DNA fibers and mounting them in a parallel array. The strategy of data collection is discussed in terms of camera design, sample environment and data collection. The methods used to correct the recorded time-of-flight data and map it into the final reciprocal space fiber diffraction dataset are also discussed. Difference Fourier maps showing the distribution of water around A-DNA calculated on the basis of these data are compared with results obtained using data recorded from hydrogenated A-DNA on D19. Since the methods used for sample preparation, data collection and data processing are fundamentally different for the monochromatic and Laue techniques, the results of these experiments also afford a valuable opportunity to independently test the data reduction and analysis techniques used in the two methods.

Crystallography↗
PubMed1994

Structure factor calculations for a side-by-side model of B-DNA.

In this paper, the side-by-side model of DNA proposed by Premilat and Albiser is investigated. The axial repeat of the model is equal to the c-axis repeat in the observed B-DNA unit cell in fibres. However, the model does not pack into the unit cell as efficiently as the B-DNA double helix does, nor is it as successful as the double helix in predicting the observed Bragg amplitudes. When the azimuthal orientations and the relative axial displacements of the two molecules in the unit cell are allowed to take general values, the best crystallographic R factor for the side-by-side model is 43.43% compared with 34.33% for the double helix. If constraints consistent with the accepted B-DNA space group, P2(1)2(1)2(1), are applied, the best R factors are 45.53% for the side-by-side model and 34.51% for the double helix. Therefore, the side-by-side model can be rejected as a possible conformation for B-DNA in crystalline fibres.

DNA↗
PubMed1992

A high angle neutron fibre diffraction study of the hydration of the A conformation of the DNA double helix.

A high angle neutron fibre diffraction study of the distribution of water around the A-form of DNA has been performed using the diffractometer D19 at the Institut Laue-Langevin, Grenoble. These experiments have exploited the ability to replace H2O surrounding the DNA by D2O so that isotopic difference Fourier maps can be computed in which peaks are identified with the distribution of water in the unit cell. All peaks of significant height have been accounted for by four families of water molecules whose positions and occupancies have been determined using least squares refinement. The coordinates of the water peaks making up each family do not deviate significantly from a regular helical arrangement with the same parameters as the DNA. Two of these families are of particular interest. The first consists of water molecules in the major groove linking successive charged phosphate oxygens along the polynucleotide chains. The second is associated with bases in the major groove and forms a central core of density along the helix axis. These two families provide a layer of hydration lining the interior wall of the major groove leaving a central channel to accommodate cations. The relationship between these observations and conformational stability is discussed.

DNA↗
PubMed1989

Neutron fibre diffraction study of DNA hydration.

Interactions with water are crucial to the conformation assumed by the DNA double helix. The location of water around the D conformation has been investigated in a neutron fibre diffraction study which shows that water is ordered in the minor groove of the DNA. The D conformation is important since its occurrence is limited to specific DNA base pair sequences which have been identified as functionally significant. This study is of particular interest because the D conformation has not been reported in single crystal studies of oligonucleotides.

DNA↗
PubMed1986

Time-resolved X-ray diffraction studies of the B in equilibrium D structural transition in the DNA double helix.

Because of the relation between topology and function, there has been much interest in the structural transitions of the various conformations of DNA polymers. The x-ray fiber diffraction analysis system at the Daresbury Synchrotron Radiation Source was used to study the reversible transition between the B and D forms of the synthetic DNA poly[d(A-T)].poly[d(A-T)]. The gradual progression of conformations between these two forms indicates that the DNA double helix does not undergo a change of handedness during this transition.

DNA↗