Directing the secondary structure of polypeptides at will: from helices to amyloids and back again?

An ageing society faces an increasing number of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Creutzfeld-Jacob disease. The deposition of amyloid fibrils is a pathogenic factor causing the destruction of neuronal tissue. Amyloid-forming proteins are mainly alpha-helical in their native conformation, but undergo an alpha-helix to beta-strand conversion before or during fibril formation. Partially unfolded or misfolded beta-sheet fragments are discussed as direct precursors of amyloids. To potentially cure neurodegenerative diseases we need to understand the complex folding mechanisms that shift the equilibrium from the functional to the pathological isoform of the proteins involved. This paper describes a novel approach that allows us to study the interplay between peptide primary structure and environmental conditions for peptide and protein folding in its whole complexity on a molecular level. This de novo designed peptide system may achieve selective inhibition of fibril formation.     

Precision measurement of neutrino oscillation parameters at INO-ICAL detector

A magnetized Iron CALorimeter (ICAL) detector at the India-based neutrino observatory (INO) is used to study neutrino oscillation sensitivity using atmospheric muon neutrino source. The ICAL detector will be able to detect muon tracks and hadron showers produced by neutrino interactions with the iron target. We have performed precision measurement analysis for the atmospheric neutrino oscillation parameters with the muon neutrino events, generated by Monte Carlo NUANCE event generator. A marginalized χ² analysis based on reconstructed neutrino energy and muon zenith angle binning scheme has been performed to determine the sensitivity for the atmospheric neutrino mixing parameters, \(\sin ^{2}\theta _{23}\) and \(| {\Delta } m^{2}_{23}|\).     

Travelling‐wave ion mobility and negative ion fragmentation of high‐mannose N‐glycans

The isomeric structure of high‐mannose N‐glycans can significantly impact biological recognition events. Here, the utility of travelling‐wave ion mobility mass spectrometry for isomer separation of high‐mannose N‐glycans is investigated. Negative ion fragmentation using collision‐induced dissociation gave more informative spectra than positive ion spectra with mass‐different fragment ions characterizing many of the isomers. Isomer separation by ion mobility in both ionization modes was generally limited, with the arrival time distributions (ATD) often showing little sign of isomers. However, isomers could be partially resolved by plotting extracted fragment ATDs of the diagnostic fragment ions from the negative ion spectra, and the fragmentation spectra of the isomers could be extracted by using ions from limited areas of the ATD peak. In some cases, asymmetric ATDs were observed, but no isomers could be detected by fragmentation. In these cases, it was assumed that conformers or anomers were being separated. Collision cross sections of the isomers in positive and negative fragmentation mode were estimated from travelling‐wave ion mobility mass spectrometry data using dextran glycans as calibrant. More complete collision cross section data were achieved in negative ion mode by utilizing the diagnostic fragment ions. Examples of isomer separations are shown for N‐glycans released from the well‐characterized glycoproteins chicken ovalbumin, porcine thyroglobulin and gp120 from the human immunodeficiency virus. In addition to the cross‐sectional data, details of the negative ion collision‐induced dissociation spectra of all resolved isomers are discussed. Copyright © 2016 John Wiley & Sons, Ltd.     

Infrared Multiphoton Dissociation Enables Top-Down Characterization of Membrane Protein Complexes and G Protein-Coupled Receptors

Membrane proteins are challenging to analyze by native mass spectrometry (MS) as their hydrophobic nature typically requires stabilization in detergent micelles that are removed prior to analysis via collisional activation. There is however a practical limit to the amount of energy which can be applied, which often precludes subsequent characterization by top-down MS. To overcome this barrier, we have applied a modified Orbitrap Eclipse Tribrid mass spectrometer coupled to an infrared laser within a high-pressure linear ion trap. We show how tuning the intensity and time of incident photons enables liberation of membrane proteins from detergent micelles. Specifically, we relate the ease of micelle removal to the infrared absorption of detergents in both condensed and gas phases. Top-down MS via infrared multiphoton dissociation (IRMPD), results in good sequence coverage enabling unambiguous identification of membrane proteins and their complexes. By contrasting and comparing the fragmentation patterns of the ammonia channel with two class A GPCRs, we identify successive cleavage of adjacent amino acids within transmembrane domains. Using gas-phase molecular dynamics simulations, we show that areas prone to fragmentation maintain aspects of protein structure at increasing temperatures. Altogether, we propose a rationale to explain why and where in the protein fragment ions are generated.     

Dynamic operation of liquid crystal cell with inherently nanogroove-featured aligned carbon nanotube sheets

The use of a highly aligned carbon nanotube (CNT) sheet as a multifunctional constituent for liquid crystal (LC) displays and electro-optic LC applications is assessed. The CNT sheet can perform a dual function: one is an alignment layer for LCs, replacing the commonly used rubbed polyimide film, and the other is a transparent conductive layer, taking the place of indium tin oxide. The hydrophobic treatment improved the adhesion quality between aligned CNT bundles and the glass substrate, which helps to preserve the inherently aligned nanogroove morphology of transparent CNT sheets. The test LC display cells, comprising 4-cyano-4′-pentylbiphenyl molecules sandwiched between CNT-sheet-on-glass substrates, demonstrate the operation characteristics comparable to that of the conventional cell under temperature variation and ac electric field of 1?kHz. The results offer a possibility of deploying multifunctional CNT-sheet alignment layers in LC-based devices, especially in the future flexible display applications.     

An Intrinsic Hydrophobicity Scale for Amino Acids and Its Application to Fluorinated Compounds

More than 100 hydrophobicity scales have been introduced, with each being based on a distinct condensed‐phase approach. However, a comparison of the hydrophobicity values gained from different techniques, and their relative ranking, is not straightforward, as the interactions between the environment and the amino acid are unique to each method. Here, we overcome this limitation by studying the properties of amino acids in the clean‐room environment of the gas phase. In the gas phase, entropic contributions from the hydrophobic effect are by default absent and only the polarity of the side chain dictates the self‐assembly. This allows for the derivation of a novel hydrophobicity scale, which is based solely on the interaction between individual amino acid units within the cluster and thus more accurately reflects the intrinsic nature of a side chain. This principle can be further applied to classify non‐natural derivatives, as shown here for fluorinated amino acid variants.