Hydration of amino acid side chains: dependence on secondary structure

Energy calculations have been used to study the hydration sitesaround the polar groups of serine, threonine and tyrosine sidechains. These hydration sites depend not only on the hybridizationof the polar group but also on the local secondary structure,the X₁ side chain torsion angle and the position of the hydroxylhydrogen atom. For tyrosine side chains, two solvent sites arefound approximately in the plane of the ring. Even for serineand threonine side chains only two minimum energy sites arefound in general of which one is in an expected position withinhydrogen bonding of the hydroxyl hydrogen atom (unless thisis blocked from interaction with solvent molecules by, for example,O_i–4 or O_i–3. The position of the second of thesesites depends not only on the position of the hydroxyl oxygenbut also on neighbouring main chain atoms to which it can alsohydrogen bond. There is good agreement with the solvent distributionsobtained from crystallographic data.     

The geometry of the knee in the sagittal plane

A geometric model of the tibio-femoral joint in the sagittal plane has been developed which demonstrates the relationship between the geometry of the cruciate ligaments and the geometry of the articular surfaces. The cruciate ligaments are represented as two inextensible fibres which, with the femur and the tibia, are analysed as a crossed four-bar linkage. The directions of the ligaments at each position of flexion are calculated. The instant centre, where the flexion axis crosses the parasagittal plane through the joint, lies at the intersection of the cruciates. It moves relative to each of the bones during flexion and extension. The successive positions of the flexion axis relative to a fixed femur and to a fixed tibia are deduced. The shapes of articular surfaces which would allow the bones to flex and extend while maintaining the ligaments each at constant length are calculated and are found to agree closely with the shapes of the natural articular surfaces. The calculated movements of the contact point between the femur and the tibia during flexion also agree well with measurements made on cadaver specimens. The outcome is a geometric simulation of the tibio-femoral joint in the sagittal plane which illustrates the central role played by the cruciate ligaments in the kinematics of the knee and which can be used for the analysis of ligament and contact forces.     

Modelling protein unfolding: hen egg-white lysozyme

A novel modelling procedure, which rapidly unfolds a protein by enhancing solvent penetration of its core, was used to investigate the unfolding pathway of hen egg-white lysozyme. Early on the unfolding pathway there is a dramatic disruption of the tertiary contacts within the protein, which decouples its domains. Subsequently, the helical domain slowly loses its compactness and the helices fluctuate rapidly. The protein then adopts a 'molten globule-like' structure in which the native beta-sheet is essentially intact. The modelled structures have properties similar to those of lysozyme's experimentally characterized partially folded states and provide insight into its complex (un)folding process. The sequence of unfolding events shows how the unfolding pathway of a multidomain protein may be most similar to its fastest, but not necessarily its dominant, folding pathway.      

NMR determination of the global structure of the 113Cd derivative of desulforedoxin: investigation of the hydrogen bonding pattern at the metal center

Desulforedoxin (Dx) is a simple homodimeric protein isolated from Desulfovibrio gigas (Dg) containing a distorted rubredoxin-like center with one iron coordinated by four cysteinyl residues (7.9 kDa with 36 amino acids per monomer). In order to probe the geometry and the H-bonding at the active site of Dx, the protein was reconstituted with 113Cd and the solution structure determined using 2D NMR methods. The structure of this derivative was initially compared with the NMR solution structure of the Zn form (Goodfellow BJ et al., 1996, J Biol Inorg Chem 1:341-353). Backbone amide protons for G4, D5, G13, L11 NH, and the Q14 NH side-chain protons, H-bonded in the X-ray structure, were readily exchanged with solvent. Chemical shift differences observed for amide protons near the metal center confirm the H-bonding pattern seen in the X-ray model (Archer M et al., 1995, J Mol Biol 251:690-702) and also suggest that H-bond lengths may vary between the Fe, Zn, and 113Cd forms. The H-bonding pattern was further probed using a heteronuclear spin echo difference (HSED) experiment; the results confirm the presence of NH-S H-bonds inferred from D2O exchange data and observed in the NMR family of structures. The presence of "H-bond mediated" coupling in Dx indicates that the NH-S H-bonds at the metal center have significant covalent character. The HSED experiment also identified an intermonomer "through space" coupling for one of the L26 methyl groups, indicating its proximity to the 113Cd center in the opposing monomer. This is the first example of an intermonomer "through space" coupling. Initial structure calculations produced subsets of NMR families with the S of C28 pointing away from or toward the L26 methyl: only the subset with the C28 sulfur pointing toward the L26 methyl could result in a "through space" coupling. The HSED result was therefore included in the structure calculations. Comparison of the Fe, Zn, and 113Cd forms of Dx suggests that the geometry of the metal center and the global fold of the protein does not vary to any great extent, although the H-bond network varies slightly when Cd is introduced. The similarity between the H-bonding pattern seen at the metal center in Dx, Rd (including H-bonded and through space-mediated coupling), and many zinc-finger proteins suggests that these H-bonds are structurally vital for stabilization of the metal centers in these proteins.     

Syndrome X and endothelial dysfunction

OBJECTIVE: Syndrome X (angina, normal coronary arteriogram and positive exercise test) remains an enigma with unexplained features and apparent conflicts of evidence. The present study addressed whether (i) the Syndrome is characterised by generalised flow-related endothelial dysfunction, (ii) myocardial thallium201 defects reflect myocardial or microvascular dysfunction, (iii) endothelial dysfunction and its consequences can be improved by oral L-arginine. METHODS: Flow-mediated brachial artery dilatation was measured by ultrasonic 'wall-tracking' in 7 Syndrome X patients, further characterised as having thallium201 defects and no known cause of endothelial dysfunction, and a normal control group. Syndrome X patients entered a 4-week randomised double-blind placebo-controlled cross-over trial of oral L-arginine (7 g twice daily), with brachial artery studies, exercise tests and technetium99 tetrafosmin scans. RESULTS: Flow-mediated dilatation was absent in Syndrome X vs. normal. Stress technetium99 tetrafosmin and thallium201 scans showed similar defects. Flow-mediated dilatation, symptom-limited exercise duration and peak oxygen consumption (VO2max) were increased but rate-pressure-product (RPP) and radionuclide defects were unchanged after L-arginine vs. placebo. CONCLUSIONS: The study supports coronary microvascular rather than myocardial dysfunction and shows loss of flow-mediated dilatation in systemic arteries. Oral L-arginine improved flow-mediated dilatation, exercise capacity and VO2max (by ca. 17%) despite unchanged RPP. The findings support generalised endothelial dysfunction. The arginine effects imply NO-mediated improvement of skeletal muscle perfusion suggesting improved homogeneity of microvascular distribution.     

Coupling efficiency calculations on an integrated l.e.d./sphere-lens source for optical fibres

The letter reports some numerical calculations on the power accepted by an optical fibre (n.a. = 0.16, radius 42.5 ?m) from an l.e.d. with an integrated hemispherical lens. It is shown that the launched power is much higher than in simple close coupling of the source, and that there is an optimum radius of 2?3 ?m for the source.     

Deoxyribonucleic acid reassociation in the classification of the 'rhodochrous' complex and allied taxa

The degree of binding was determined between DNA preparations from gordonae and rhodochrous strains and uracil-labelled DNA from five reference strains, Nocardia asteroides NK20, N. pellegrino PII, Gordona bronchialis TI, G. terrae T5 and rhodochrous strain R90. Most of the rhodochrous and pellegrino strains fell into one of two genetically homogeneous taxa. The nucleotide sequence homology data also suggested that G. bronchialis, G. rubra, and more equivocally G. terrae, formed distinct species. However, the values for DNA relatedness between these species, and between then and the rhodochrous homology groups, were comparatively low. Only a small degree of nucleotide sequence homology was found between the N. asteroides reference system and the rest of the taxa studied. The nucleotide composition of the DNA preparations from 29 of the 30 test strains fell between 63 and 69 mol% guanine plus cytosine.     

Optoelectronic component arrays for optical interconnection ofcircuits and subsystems

The design and performance of arrays of hybrid optoelectronic detector and modulator elements for use as optical input and output pads for chip- and board-level optical interconnects are discussed. The application of these interface arrays to specific VLSI circuits is discussed, illustrating the potential improvements in performance levels. This solder bond technique is capable of very accurate component positioning at points across the entire surface of the VLSI circuit, so that precise alignment to the optical pathways can be envisaged with optical signals taken from or delivered to any position on the chip. Measurements presented indicate that submicron positioning can be achieved. In particular, a fabrication-tolerant modulator design incorporating a chirped semiconductor mirror is reported     

Acoustic beam splitter for infrared lasers

A method for noninterference sampling of high-power CO2laser beams is described. The technique employs an ultrasonic diffraction grating generated in the air path across a laser beam. A very small fraction (sim10^{-7}) of the main beam is diffracted through a small angle (sim2deg) on either side. Profiles of Gaussian and "donut" modes from low-power CO2lasers were obtained with the acoustic beam splitter.     

Dependence of electrostatic charging currents on fluid properties

The dependence of the electrical charging of hydrocarbons on the chemical nature of non-hydrocarbon additives has been investigated. An improved apparatus and technique allowed the authors to obtain data for new fluid systems over a wide range of solution conductivities and flow velocities. Currents and voltages have been measured from insulated stainless steel tubes, for different concentrations of polar species in hydrocarbon solutions, for Reynolds numbers of 1800 to 35,000. Recent electrification theories explain the charging process on the basis of a diffusion-controlled process. The magnitudes of the charging currents can be predicted using the usual mass transfer analogies. Experimental results, obtained for different polar additives studied, agreed with the theory. The sign of the measured current is not predicted theoretically. Potentials of both signs are observed. The particular sign obtained seems to be determined by the chemical nature of the polar additive. Different additives of similar chemical structure all give one sign.