Molecular insights into aggregates made of amphiphilic Fmoc-tetrapeptides

Pre-assembled aggregates made of Fmoc-conjugated RGDS and GRDS peptides, where Fmoc refers to fluorenylmethoxycarbonyl, have been investigated using atomistic molecular dynamics simulations. The structural characteristics of twelve different models involving two sheets packed with the Fmoc-aligned or with the charged side groups oriented face-to-face, each one containing seven explicit peptide molecules arranged in parallel or antiparallel, have been evaluated for each Fmoc-tetrapeptide. Structural criteria have been used to select the preferred assembly for each Fmoc-tetrapeptide. The two peptides have been found to prefer b-sheet assemblies with a parallel configuration under simulated low concentration conditions. Furthermore, the assembly is dominated by the interactions among Fmoc units. The overall results provide a complete atomistic view of the interactions between Fmoc-peptide molecules comprised within the same sheet or in different sheets that was not achieved experimentally.

The cyclical relations between traded property stock prices and aggregate time-series

This paper examines the cyclical regularities of macroeconomic, financial and property market aggregates in relation to the property stock price cycle in the UK. The Hodrick Prescott filter is employed to fit a long-term trend to the raw data, and to derive the short-term cycles of each series. It is found that the cycles of consumer expenditure, total consumption per capita, the dividend yield and the long-term bond yield are moderately correlated, and mainly coincident, with the property price cycle. There is also evidence that the nominal and real Treasury Bill rates and the interest rate spread lead this cycle by one or two quarters, and therefore that these series can be considered leading indicators of property stock prices. This study recommends that macroeconomic and financial variables can provide useful information to explain and potentially to forecast movements of property-backed stock returns in the UK.

The three-dimensional morphology of simulated and observed convective storms over southern England

A set of high-resolution radar observations of convective storms has been collected to evaluate such storms in the UK Met Office Unified Model during the DYMECS project (Dynamical and Microphysical Evolution of Convective Storms). The 3-GHz Chilbolton Advanced Meteorological Radar was set up with a scan-scheduling algorithm to automatically track convective storms identified in real-time from the operational rainfall radar network. More than 1,000 storm observations gathered over fifteen days in 2011 and 2012 are used to evaluate the model under various synoptic conditions supporting convection. In terms of the detailed three-dimensional morphology, storms in the 1500-m grid-length simulations are shown to produce horizontal structures a factor 1.5–2 wider compared to radar observations. A set of nested model runs at grid lengths down to 100m show that the models converge in terms of storm width, but the storm structures in the simulations with the smallest grid lengths are too narrow and too intense compared to the radar observations. The modelled storms were surrounded by a region of drizzle without ice reflectivities above 0 dBZ aloft, which was related to the dominance of ice crystals and was improved by allowing only aggregates as an ice particle habit. Simulations with graupel outperformed the standard configuration for heavy-rain profiles, but the storm structures were a factor 2 too wide and the convective cores 2 km too deep.

Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif

The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers’ disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly “nanodisc” structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/ Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates.

Self-assembly of telechelic tyrosine end-capped PEO and poly(alanine) polymers in aqueous solution

The self-assembly in aqueous solution of three novel telechelic conjugates comprising a central hydrophilic polymer and short (trimeric or pentameric) tyrosine end-caps has been investigated. Two of the conjugates have a central poly(oxyethylene) (polyethylene oxide, PEO) central block with different molar masses. The other conjugate has a central poly(l-alanine) (PAla) sequence in a purely amino-acid based conjugate. All three conjugates self-assemble into β-sheet based fibrillar structures, although the fibrillar morphology revealed by cryogenic-TEM is distinct for the three polymers—in particular the Tyr5-PEO6k-Tyr5 forms a population of short straight fibrils in contrast to the more diffuse fibril aggregates observed for Tyr5-PEO2k-Tyr5 and Tyr3-PAla-Tyr3. Hydrogel formation was not observed for these samples (in contrast to prior work on related systems) up to quite high concentrations, showing that it is possible to prepare solutions of peptide–polymer-peptide conjugates with hydrophobic end-caps without conformational constraints associated with hydrogelation. The Tyr5-PEO6k-Tyr5 shows significant PEO crystallization upon drying in contrast to the Tyr5-PEO2k-Tyr5 conjugate. Our findings point to the remarkable ability of short hydrophobic peptide end groups to modulate the self-assembly properties of polymers in solution in model peptide-capped “associative polymers”. Retention of fluidity at high conjugate concentration may be valuable in potential future applications of these conjugates as bioresponsive or biocompatible materials, for example exploiting the enzyme-responsiveness of the tyrosine end-groups