Quantitative measurement of protease ligand conformation

The tendency for protease ligands to bind in an extended conformation has been suggested as an important factor for the identification of compounds of medicinal importance. Here we present a novel graph-theoretical method giving a quantitative measure of ligand conformation, and through application of this method to a representative set of protease ligands in bound and unbound conformations, derive the result that protease ligands are more extended in conformation when in their bound state. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Enhanced Light‐Harvesting Capacity by Micellar Assembly of Free Accessory Chromophores and LH1‐like Antennas

Biohybrid light‐harvesting antennas are an emerging platform technology with versatile tailorability for solar‐energy conversion. These systems combine the proven peptide scaffold unit utilized for light harvesting by purple photosynthetic bacteria with attached synthetic chromophores to extend solar coverage beyond that of the natural systems. Herein, synthetic unattached chromophores are employed that partition into the organized milieu (e.g. detergent micelles) that house the LH1‐like biohybrid architectures. The synthetic chromophores include a hydrophobic boron‐dipyrrin dye (A1) and an amphiphilic bacteriochlorin (A2), which transfer energy with reasonable efficiency to the bacteriochlorophyll acceptor array (B875) of the LH1‐like cyclic oligomers. The energy‐transfer efficiencies are markedly increased upon covalent attachment of a bacteriochlorin (B1 or B2) to the peptide scaffold, where the latter likely acts as an energy‐transfer relay site for the (potentially diffusing) free chromophores. The efficiencies are consistent with a Förster (through‐space) mechanism for energy transfer. The overall energy‐transfer efficiency from the free chromophores via the relay to the target site can approach those obtained previously by relay‐assisted energy transfer from chromophores attached at distant sites on the peptides. Thus, the use of free accessory chromophores affords a simple design to enhance the overall light‐harvesting capacity of biohybrid LH1‐like architectures.     

The Internet, evolutionary variational inequalities, and the time-dependent Braess paradox

In this paper, we develop an evolutionary variational inequality model of the Internet with multiple classes of traffic and demonstrate its utility through the formulation and solution of a time-dependent Braess paradox. The model can handle time-dependent changes in demand as a consequence of developing news stories, following, for example, natural disasters or catastrophes or major media events. The model can also capture the time-varying demand for Internet resources during a regular weekday with its more regular rhythm of work and breaks. In addition, the model includes time-varying capacities on the route flows due to, for example, government interventions or network-type failures.     

Development and applications of a sample controlled DSC system

The development of a new sample controlled thermal analysis technique based on a heat flux DSC is described. The performance of the system is demonstrated by studies on the decomposition of sodium bicarbonate and the oxidation of a copper impregnated carbon. The ability of the technique to study reactions which take place without a change in mass is illustrated by the curing of an epoxy resin with a polyaminoamide hardener.     

Connectivity and binding‐site recognition: Applications relevant to drug design

Here, we describe a family of methods based on residue–residue connectivity for characterizing binding sites and apply variants of the method to various types of protein–ligand complexes including proteases, allosteric‐binding sites, correctly and incorrectly docked poses, and inhibitors of protein–protein interactions. Residues within ligand‐binding sites have about 25% more contact neighbors than surface residues in general; high‐connectivity residues are found in contact with the ligand in 84% of all complexes studied. In addition, a k‐means algorithm was developed that may be useful for identifying potential binding sites with no obvious geometric or connectivity features. The analysis was primarily carried out on 61 protein–ligand structures from the MEROPS protease database, 250 protein–ligand structures from the PDBSelect (25%), and 30 protein–protein complexes. Analysis of four proteases with crystal structures for multiple bound ligands has shown that residues with high connectivity tend to have less variable side‐chain conformation. The relevance to drug design is discussed in terms of identifying allosteric‐binding sites, distinguishing between alternative docked poses and designing protein interface inhibitors. Taken together, this data indicate that residue–residue connectivity is highly relevant to medicinal chemistry. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Electron-transfer and chemical reactivity following collisions of Ar with C2H2

The reaction between Ar²⁺ and C₂H₂ has been studied, at centre-of-mass collision energies ranging from 3 to 7 eV, using a position-sensitive coincidence technique to detect the monocation pairs, which are formed. Sixteen different reaction channels generating pairs of monocations have been observed, these channels arise from double-electron-transfer, single-electron-transfer and chemical reactions forming ArC⁺. Examination of the scattering diagrams and energetic information extracted from the coincidence data indicate that double-electron-transfer is a direct process, which does not involve a collision complex, and the derived energetics point towards a concerted, not stepwise, mechanism for the two-electron-transfer. As is commonly observed, single-electron-transfer from C₂H₂ to Ar²⁺ takes place via a direct mechanism, again not involving complexation. Most of the C₂H₂⁺ products that are formed in the single-electron-transfer reactions possess significant (12–15 eV) internal energy and fragment rapidly within the electric field of the partner Ar⁺ ion. The chemical reactions appear to proceed via a direct mechanism involving the initial formation of ArCH⁺, which subsequently fragments to form ArC⁺.     

A note on “New travelling wave solutions to the Ostrovsky equation”

In a recent paper by Ya?ar [E. Ya?ar, New travelling wave solutions to the Ostrovsky equation, Appl. Math. Comput. 216 (2010), 3191-3194], ‘new’ travelling-wave solutions to the transformed reduced Ostrovsky equation are presented. In this note it is shown that some of these solutions are disguised versions of known solutions.     

A supernodal formulation of vertex colouring with applications in course timetabling

For many problems in scheduling and timetabling, the choice of a mathematical programming formulation is determined by the formulation of the graph colouring component. This paper briefly surveys seven known integer programming formulations of vertex colouring and introduces a new approach using “supernodes”.