CyBase: a database of cyclic protein sequences and structures, with applications in protein discovery and engineering

CyBase was originally developed as a database for backbone-cyclized proteins, providing search and display capabilities for sequence, structure and function data. Cyclic proteins are interesting because, compared to conventional proteins, they have increased stability and enhanced binding affinity and therefore can potentially be developed as protein drugs. The new CyBase release features a redesigned interface and internal architecture to improve user-interactivity, collates double the amount of data compared to the initial release, and hosts a novel suite of tools that are useful for the visualization, characterization and engineering of cyclic proteins. These tools comprise sequence/structure 2D representations, a summary of grafting and mutation studies of synthetic analogues, a study of N- to C-terminal distances in known protein structures and a structural modelling tool to predict the best linker length to cyclize a protein. These updates are useful because they have the potential to help accelerate the discovery of naturally occurring cyclic proteins and the engineering of cyclic protein drugs. The new release of CyBase is available at http://research1t.imb.uq.edu.au/cybas

Electric Vehicles in Imperfect Electricity Markets: A German Case Study

We analyze the impacts of a hypothetical fleet of plug-in electric vehicles on the imperfectly competitive German electricity market with a game-theoretic model. Electric vehicles bring both additional demand and additional storage capacity to the market. We determine their effects on prices, welfare, and electricity generation for various cases with different players being in charge of vehicle operations. We find that vehicle loading increases generator profits, but decreases consumer surplus. If excess vehicle batteries can be used for storage, welfare results are reversed: generating firms suffer from the price-smoothing effect of additional storage, whereas consumers benefit despite increasing overall demand. Results however depend on the player being in charge of storage operations, and on battery degradation costs. Strategic players tend to underutilize the storage capacity of the vehicle fleet, which may have negative welfare implications. In contrast, we find a small market power mitigating effect of electric vehicle recharging on oligopolistic generators. Overall, electric vehicles are unlikely to be a relevant source of market power in Germany

Structure and activity of the leaf-specific cyclotide vhl-2

Cyclotides are plant-derived macrocyclic peptides with potential applications in the pharmaceutical and agricultural industries. In addition to their presumed natural function as host-defence peptides arising from their insecticidal activity, their other biological activities include antimicrobial, haemolytic, and cytotoxic activities, but at present, only limited information is available on the structural and chemical features that are important for these various activities. In the current study, we determined the three-dimensional structure of vhl-2, a leaf-specific cyclotide. Although the characteristic cyclic cystine knot fold of other cyclotides is maintained in vhl-2, it has more potent haemolytic activity than well-characterized cyclotides such as kalata B1 and kalata B8. Analysis of surface hydrophobicity and haemolytic activity for a range of cyclotides indicates a correlation between them, with increasing hydrophobicity resulting in increased haemolytic activity. This correlation is consistent with membrane binding being a vital step in mediating the various cytotoxic activities of cyclotides. The gene sequence for vhl-2 was determined and indicates that vhl-2 is processed from a multidomain precursor protein that also encodes the cyclotide cycloviolacin H3