Characterization of the stereochemical selectivity of beta-hairpin formation by molecular dynamics simulations

The stability of secondary structure motifs found in proteins is influenced by the choice of the configuration of the chiral centers present in the amino acid residues (i.e., D vs L). Experimental studies showed that the structural properties of the tetrapeptide (L)V(L)P(L)A(L)L (all-L) are drastically altered upon mutating the L-proline and the L-alanine by their d-enantiomers [J. Am. Chem. Soc. 1996, 118, 6975]. The all-L diastereomer is unstructured, experiencing little or no beta-hairpin formation, while the (L)V(D)P(D)A(L)L peptide exhibits a substantial population of beta-hairpin conformation. In this study, we perform molecular dynamics simulations to investigate the folding propensity of these two model peptides. The results confirm the experimental findings, namely, that the presence of d-amino acids in the loop region strongly induces beta-hairpin formation (a population increase from about 1.5% to 50% is observed). The major factor determining the different behavior is found to be the large difference in energy between the two diastereomers, approximately 22 kJ/mol, when they adopt a beta-hairpin structure. The higher energy observed for the all-L peptide is a consequence of none-ideal hydrogen bond formation and of steric repulsions. The results suggest that selective incorporation of D-amino acids in proteins can be used to enhance certain secondary structure elements. The kinetic behavior of the folding process observed in the simulations is also investigated. We find that the decay rate of the folded structure fits to a biexponential function, suggesting that the folding/unfolding process of a beta-hairpin is governed by two different mechanisms.     

A predictive pattern of computed barriers for C-h hydroxylation by compound I of cytochrome p450

The communication presents DFT calculations of 10 different C-H hydroxylation barriers by the active species of the enzyme cytochrome P450. The work demonstrates the existence of an excellent barrier-bond energy correlation. The so-obtained equation of the straight line is demonstrated to be useful for predicting barriers of related C-H activation processes, as well as for assessing barrier heights within the protein environment. This facility is demonstrated be estimating the barrier of camphor hydroxylation by P450cam.     

Tactical store delivery planning

We describe a system for tactical planning of store deliveries that has been developed for a major US retailer. The retailer operates several distribution centres (DCs) and has over one thousand stores. The system is used for planning weekly fixed truck routes for store deliveries at minimal cost, where each route visits several stores, taking into account tight daily workload constraints in the DCs, limited daily transportation capacity, and store requirements. Initial results show a saving potential of 1–5%, amounting to several million US dollars annually, and truncation of the planning process from weeks to hours.     

Detection and Identification of Alkylating Agents by Using a Bioinspired “Chemical Nose”

Alkylating agents are simple and reactive molecules that are commonly used in many and diverse fields such as organic synthesis, medicine, and agriculture. Some highly reactive alkylating species are also being used as blister chemical‐warfare agents. The detection and identification of alkylating agents is not a trivial issue because of their high reactivity and simple structure. Herein, we report on a new multispot luminescence‐based approach to the detection and identification of alkylating agents. In order to demonstrate the potential of the approach, seven π‐conjugated oligomers and polymers bearing nucleophilic pyridine groups, 1 – 7 , were adsorbed onto a solid support and exposed to vapors of alkylators 8 – 15 . The alkylation‐induced color‐shift patterns of the seven‐spot array allow clear discrimination of the different alkylators. The spots are sensitive to minute concentrations of alkylators and, because the detection is based on the formation of new covalent bonds, these spots saturate at about 50 ppb.     

Nonadiabatic chemical reaction triggered by electron photodetachment: an ab initio quantum dynamical study

Dynamics following electron photodetachment in a complex of a chloride anion with ammonia is explored by a combination of electronic structure and quantum dynamical methods. This system serves as a prototype for investigating a hitherto unexplored class of chemical reactions-nonadiabatic proton transfer triggered by a detachment of an electron. All the reactive and nonreactive channels of this process are characterized and the respective quantum yields are presented.     

Long term behavior of lithographically prepared in vitro neuronal networks

We measured the long term spontaneous electrical activity of neuronal networks with different sizes, grown on lithographically prepared substrates and recorded with multi-electrode-array technology. The time sequences of synchronized bursting events were used to characterize network dynamics. All networks exhibit scale-invariant Lévy distributions and long-range correlations. These observations suggest that different-size networks self-organize to adjust their activities over many time scales. As predictions of current models differ from our observations, this calls for revised models.     

Electrochemically Predicting Phenolic Substrates’ Suitability for Detection by Amperometric Laccase Biosensors

In this article, a rapid, simple method of electrochemically predicting a given phenolic substrate’s ability to be detected via amperometric laccase biosensors is proposed. Ten selected substrates were analysed by cyclic voltammetry and the relevant electrochemical parameters compared to biosensor kinetic parameters produced through amperometric detection of these substrates. The two major findings of this study were that biosensor detection sensitivities were found to correlate to: (1) peak oxidation potential of a substrate at unmodified electrodes and (2) the apparent Michaelis? Menten constant, K_m, of the biosensor‐substrate system, once corrections accounting for the relative differences in electroreducible product yield are made.     

Structural Transformation of SnS2 to SnS by Mo Doping Produces Electro/Photocatalyst for Hydrogen Production

SnS and SnS₂ are layered semiconductors, with potential promising properties for electro- and photocatalytic hydrogen (H₂) production. The vast knowledge in preparation and modification of layered structures was still not employed successfully in this system to fully maximize its potential. Here, the first report of structural transformation of SnS₂ into SnS with Mo-doping as a bifunctional catalyst for the hydrogen evolution reaction (HER) is reported. The structural phase transition optimized the properties of the material, providing a more delicate morphology with additional catalytic sites. The electrochemical studies showed overpotential of 377 mV at 10 mA cm⁻² for HER with Tafel slopes of 100 mV dec⁻¹ in 0.5 m H₂SO₄ for 10 % Mo-SnS. The same structure acts as an efficient photocatalyst in the generation of H₂ from water under visible illumination with rate of 0.136 mmol g⁻¹ h⁻¹ of H₂, which is 20 times higher than pristine SnS₂ under visible light.     

A Polynomial Number of Random Points Does Not Determine the Volume of a Convex Body

We show that there is no algorithm which, provided a polynomial number of random points uniformly distributed over a convex body in ℝ ⁿ , can approximate the volume of the body up to a constant factor with high probability.