Applications of NMR in drug design: Sructure-activity relationships in disulfide-rich peptides

NMR is a powerful technique for determining structures of biologically active molecules in solution. In recent years. our laboratory has focussed on the structure determination of small disulfide-rich proteins from both plants and animals which are valuable targets in drug design applications. This article will review these structural studies and their implications in drug design.

Changes in quantum efficiency of Photosystem II of symbiotic dinoflagellates of corals after heat stress, and of bleached corals sampled after the 1998 Great Barrier Reef mass bleaching event Ross J. Jones , Selina Ward, Affendi Yang Amri and Ove Hoegh-Guldberg

Pulse-amplitude-modulation chlorophyll fluorometry was used to examine changes in dark-adapted F-v/F-m of endosymbiotic dinoflagellate microalgae within the tissues of the temperate coral Plesiastrea versipora exposed to elevated seawater temperature. The F-v/F-m was markedly reduced following exposure of corals to 28 degrees C for 48 h. When corals were returned to ambient (24 degrees C) conditions, F-v/F-m increased in an initial rapid and then secondary slower phase. Tissue discolouration (coral bleaching), caused by a significant decrease in the density of algae, was observed during the first 2-3 days of the recovery period. After 14 days, F-v/F-m was still significantly lower than in control corals. The recovery of F-v/F-m is discussed in terms of repair processes within the symbiotic algae, division of healthy algae and also the selective removal of photo-damaged dinoflagellates. Under field conditions, bleached corals sampled at Heron Island Reef during a bleaching event had significantly lower F-v/F-m than non-bleached colonies; four months after the bleaching event, there were no differences in F-v/F-m or algal density in corals marked as having bleached or having shown no signs of colour loss. The results of this laboratory and field study are consistent with the hypothesis that an impairment of photosynthesis occurs during heat-stress, and is the underlying cause of coral bleaching.

Characterization of the sequential non-covalent and covalent interactions of the antitumour antibiotic hedamycin with double stranded DNA by NMR spectroscopy

Hedamycin, a member of the pluramycin class of antitumour antibiotics, consists of a planar anthrapyrantrione chromophore to which is attached two aminosugar rings at one end and a bisepoxide-containing sidechain at the other end, Binding to double-stranded DNA is known to involve both reversible and non-reversible modes of interaction. As a part of studies directed towards elucidating the structural basis for the observed 5'-pyGT-3' sequence selectivity of hedamycin, we conducted one-dimensional NMR titration experiments at low temperature using the hexadeoxyribonucleotide duplexes d(CACGTG)(2) and d(CGTACG)(2). Spectral changes which occurred during these titrations are consistent with hedamycin initially forming a reversible complex in slow exchange on the NMR timescale and binding through intercalation of the chromophore. Monitoring of this reversible complex over a period of hours revealed a second type of spectral change which corresponds with formation of a non-reversible complex. Copyright (C) 1999 John Wiley & Sons, Ltd.

Quantum and classical chaos for a single trapped ion

In this paper we investigate the quantum and classical dynamics of a single trapped ion subject to nonlinear kicks derived from a periodic sequence of Gaussian laser pulses. We show that the classical system exhibits: diffusive growth in the energy, or heating,'' while quantum mechanics suppresses this heating. This system may be realized in current single trapped-ion experiments with the addition of near-field optics to introduce tightly focused laser pulses into the trap.

Quantum controlled-NOT gate with 'hot' trapped ions

We present a novel method of performing quantum logic gates in trapped ion quantum computers which does not require the ions to be cooled down to the ground state of their vibrational modes, thereby avoiding one of the principal experimental difficulties encountered in realizing this technology. Our scheme employs adiabatic passages and a phase shift conditional on the phonon number state.

A new approach to current and noise in double quantum dot systems

We use a quantum master equation to describe transport in double-dot devices. The coherent dot-to-dot coupling affects the noise spectra strongly. For phonon-assisted tunneling, the calculated current spectra are consistent with those of experiments. The model shows that quantum stochastic theory may he applied to some advantage in mesoscopic electronic systems. (C) 2000 Elsevier Science B.V. All rights reserved.

Exactly solvable quantum spin ladders associated with the orthogonal and symplectic Lie algebras

We extend the results of spin ladder models associated with the Lie algebras su(2(n)) to the case of the orthogonal and symplectic algebras o(2(n)), sp(2(n)) where n is the number of legs for the system. Two classes of models are found whose symmetry, either orthogonal or symplectic, has an explicit n dependence. Integrability of these models is shown for an arbitrary coupling of XX-type rung interactions and applied magnetic field term.

Identification of initiation sites for T4 lysozyme folding using CD and NMR spectroscopy of peptide fragments

Using CD and 2D H-1 NMR spectroscopy, we have identified potential initiation sites for the folding of T4 lysozyme by examining the conformational preferences of peptide fragments corresponding to regions of secondary structure. CD spectropolarimetry showed most peptides were unstructured in water, but adopted partial helical conformations in TFE and SDS solution. This was also consistent with the H-1 NMR data which showed that the peptides were predominantly disordered in water, although in some cases, nascent or small populations of partially folded conformations could be detected. NOE patterns, coupling constants, and deviations from random coil Her chemical shift values complemented the CD data and confirmed that many of the peptides were helical in TFE and SDS micelles. In particular, the peptide corresponding to helix E in the native enzyme formed a well-defined helix in both TFE and SDS, indicating that helix E potentially forms an initiation site for T4 lysozyme folding. The data for the other peptides indicated that helices D, F, G, and H are dependent on tertiary interactions for their folding and/or stability. Overall, the results from this study, and those of our earlier studies, are in agreement with modeling and IID-deuterium exchange experiments, and support an hierarchical model of folding for T4 lysozyme.

Multidimensional quantum solitons with nondegenerate parametric interactions: Photonic and Bose-Einstein condensate environments

We consider the quantum theory of three fields interacting via parametric and repulsive quartic couplings. This can be applied to treat photonic chi((2)) and chi((3)) interactions, and interactions in atomic Bose-Einstein condensates or quantum Fermi gases, describing coherent molecule formation together with a-wave scattering. The simplest two-particle quantum solitons or bound-state solutions of the idealized Hamiltonian, without a momentum cutoff, are obtained exactly. They have a pointlike structure in two and three dimensions-even though the corresponding classical theory is nonsingular. We show that the solutions can be regularized with a momentum cutoff. The parametric quantum solitons have much more realistic length scales and binding energies than chi((3)) quantum solitons, and the resulting effects could potentially be experimentally tested in highly nonlinear optical parametric media or interacting matter-wave systems. N-particle quantum solitons and the ground state energy are analyzed using a variational approach. Applications to atomic/molecular Bose-Einstein condensates (BEC's) are given, where we predict the possibility of forming coupled BEC solitons in three space dimensions, and analyze superchemistry dynamics.

Quantum interference in the fluorescence of a molecular system

It has been observed experimentally [H.R. Xia, C.Y. Ye, and S.Y. Zhu, Phys. Rev. Lett. 77, 1032 (1996)] that quantum interference between two molecular transitions can lead to a suppression or enhancement of spontaneous emission. This is manifest in the fluorescent intensity as a function of the detuning of the driving field from the two-photon resonance condition. Here we present a theory that explains the observed variation of the number of peaks with the mutual polarization of the molecular transition dipole moments. Using master equation techniques we calculate analytically as well as numerically the steady-state fluorescence, and find that the number of peaks depends on the excitation process. If the molecule is driven to the upper levels by a two-photon process, the fluorescent intensity consists of two peaks regardless of the mutual polarization of the transition dipole moments. Lf the excitation process is composed of both a two-step, one-photon process and a one-step, two-photon process, then there are two peaks on transitions with parallel dipole moments and three peaks on transitions with antiparallel dipole moments. This latter case is in excellent agreement with the experiment.

Disagreement between correlations of quantum mechanics and stochastic electrodynamics in the damped parametric oscillator

Intracavity and external third order correlations in the damped nondegenerate parametric oscillator are calculated for quantum mechanics and stochastic electrodynamics (SED), a semiclassical theory. The two theories yield greatly different results, with the correlations of quantum mechanics being cubic in the system's nonlinear coupling constant and those of SED being linear in the same constant. In particular, differences between the two theories are present in at least a mesoscopic regime. They also exist when realistic damping is included. Such differences illustrate distinctions between quantum mechanics and a hidden variable theory for continuous variables.

Atoms in an amplitude-modulated standing wave - dynamics and pathways to quantum chaos

Cold rubidium atoms are subjected to an amplitude-modulated far-detuned standing wave of light to form a quantum-driven pendulum. Here we discuss the dynamics of these atoms. Phase space resonances and chaotic transients of the system exhibit dynamics which can be useful in many atom optics applications as they can be utilized as means for phase space state preparation. We explain the occurrence of distinct peaks in the atomic momentum distribution, analyse them in detail and give evidence for the importance of the system for quantum chaos and decoherence studies.

Quantum chaos in atom optics

I shall discuss the quantum and classical dynamics of a class of nonlinear Hamiltonian systems. The discussion will be restricted to systems with one degree of freedom. Such systems cannot exhibit chaos, unless the Hamiltonians are time dependent. Thus we shall consider systems with a potential function that has a higher than quadratic dependence on the position and, furthermore, we shall allow the potential function to be a periodic function of time. This is the simplest class of Hamiltonian system that can exhibit chaotic dynamics. I shall show how such systems can be realized in atom optics, where very cord atoms interact with optical dipole potentials of a far-off resonance laser. Such systems are ideal for quantum chaos studies as (i) the energy of the atom is small and action scales are of the order of Planck's constant, (ii) the systems are almost perfectly isolated from the decohering effects of the environment and (iii) optical methods enable exquisite time dependent control of the mechanical potentials seen by the atoms.

C-13-NMR, H-1-NMR, and FT-Raman study of radiation-induced modifications in radiation dosimetry polymer gels

H-1- and C-13-NMR spectroscopy and FT-Raman spectroscopy are used to investigate the properties of a polymer gel dosimeter post-irradiation. The polymer gel (PACT) is composed of acrylamide, N,N'-methylene-bisacrylamide, gelatin, and water. The formation of a polyacrylamide network within the gelatin matrix follows a dose dependence nonlinearly correlated to the disappearance of the double bonds from the dissolved monomers within the absorbed dose range of 0-50 Gy. The signal from the gelatin remains constant with irradiation. We show that the NMR spin-spin relaxation times (T-2) of PAGs irradiated to up to 50 Gy measured in a NMR spectrometer and a clinical magnetic resonance imaging scanner can be modeled using the spectroscopic intensity of the growing polymer network. More specifically, we show that the nonlinear T-2 dependence against dose can be understood in terms of the fraction of protons in three different proton pools. (C) 2000 John Wiley & Sons, Inc.

Absorptive quantum measurements via coherently coupled quantum dots

We propose an absorptive measurement scheme via coupled quantum dots based on studies of the quantum dynamics of coherently coupled dots. The system is described through a Markov master equation that is related to a measurable quantity, the current. We analyse the measurement configuration and calculate the correlations and noise spectra beyond the adiabatic approximation.