Molecular dynamics simulations of proteins and peptides: from folding to drug design

Computer simulations of proteins, lipids and nucleic acids at equilibrium have become essentially routine. However, the fact remains that complete sampling of conformational space continues to be a bottle-neck in the field. The challenge for the future is to overcome such problems and use computational approaches to understand recognition and spontaneous self-organization in biomolecular systems (folding, aggregation and assembly of complexes), processes that cannot be directly observed experimentally. In this review, examples illustrating the extent to which simulations can be used to understand these phenomena in biomolecular systems will be presented along with examples of methodological developments to increase our physical understanding of the processes. The study cases will cover the problems of peptide-receptor recognition and the use of the information obtained for the design of new non-peptidic ligands; the study of the folding mechanism of small proteins and finally the study of the initial stages of peptide self-aggregation.     

Towards measurement of homonuclear dipolar couplings in 1H solid-state NMR: recoupling with a rotor-synchronized decoupling scheme

We describe a magic-angle spinning NMR experiment for (1)H-(1)H homonuclear dipole-dipole coupling estimations in organic solids. The methodology involves reintroducing dipolar interactions with rotor-synchronized homonuclear decoupling pulse sequences. Frequency-selective DANTE pulses are used to isolate a specific spin pair from a natural isotopic abundance sample. The coupling of interest, between the selected spin pair, may be extracted by a non linear least-squares fit of the experimentally observed modulation of the signal intensity to an exact analytical formula. The experiment is demonstrated on natural isotopic abundance glycine and alanine powder samples.     

Applications of dewetting in micro and nanotechnology

Dewetting is a spontaneous phenomenon where a thin film on a surface ruptures into an ensemble of separated objects, like droplets, stripes, and pillars. Spatial correlations with characteristic distance and object size emerge spontaneously across the whole dewetted area, leading to regular motifs with long-range order. Characteristic length scales depend on film thickness, which is a convenient and robust technological parameter. Dewetting is therefore an attractive paradigm for organizing a material into structures of well-defined micro- or nanometre-size, precisely positioned on a surface, thus avoiding lithographical processes. This tutorial review introduces the reader to the physical-chemical basis of dewetting, shows how the dewetting process can be applied to different functional materials with relevance in technological applications, and highlights the possible strategies to control the length scales of the dewetting process.     

Facing unexpected reactivity paths with Zr(IV)-pyridylamido polymerization catalysts

This work provides original insights to the better understanding of the complex structure-activity relationship of Zr(IV)-pyridylamido-based olefin polymerization catalysts and highlights the importance of the metal-precursor choice (Zr(NMe(2))(4) vs. Zr(Bn)(4)) to prepare precatalysts of unambiguous identity. A temperature-controlled and reversible σ-bond metathesis/protonolysis reaction is found to take place on the Zr(IV)-amido complexes in the 298-383 K temperature range, changing the metal coordination sphere dramatically (from a five-coordinated tris-amido species stabilized by bidentate monoanionic {N,N(-)} ligands to a six-coordinated bis-amido-mono-amino complexes featured by tridentate dianionic {N(-),N,C(-)} ligands). Well-defined neutral Zr(IV)-pyridylamido complexes have been prepared from Zr(Bn)(4) as metal source. Their cationic derivatives [Zr(IV) N(-),N,C(-)}Bn](+)[B(C(6)F(5))(4)](-) have been successfully applied to the room-temperature polymerization of 1-hexene with productivities up to one order of magnitude higher than those reported for the related Hf(IV) state-of-the-art systems. Most importantly, a linear increase of the poly(1-hexene) M(n) values (30-250 kg mol(-1)) has been observed upon catalyst aging. According to that, the major active species (responsible for the increased M(n) polymer values) in the aged catalyst solution, has been identified.     

Towards a human proteomics atlas

Proteomics research has taken up an increasingly important role in life sciences over the past few years. Due to a strong push from publishers and funders alike, the community has also started to freely share its data in earnest, making use of public repositories such as the highly popular PRIDE database at EMBL-EBI. Reuse of these publicly available data has so far been confined to rather specific, targeted reanalyses, but this limited reuse is set to expand dramatically as repositories continue to grow exponentially. Examples of large-scale reuse are readily found in other omics disciplines, where more comprehensive public data have already accumulated over longer periods. Here, a typical example of integrative data reuse is provided by the construction of so-called expression atlases. We here therefore investigate the issues involved in using the human data currently stored in the PRIDE database to construct a robust, tissue-specific protein expression atlas from tandem-MS based label-free quantification.     

Electronic and structural shell closure in AgCu and AuCu nanoclusters

The structures of AgCu clusters containing 40 atoms are investigated. The most promising structural families (fcc clusters, capped decahedra, and two types of capped polyicosahedra) are singled out by means of global optimization techniques within an atom-atom potential model. Then, representative clusters of each family are relaxed by means of density-functional methods. It is shown that, for a large majority of compositions, a complex interplay of geometric and electronic shell-closure effects stabilizes a specific polyicosahedral family, whose clusters are much lower in energy and present large HOMO-LUMO gaps. Within this family, geometric and quantum effects concur to favor magic structures associated with core-shell chemical ordering and high symmetry, so that these clusters are very promising from the point of view of their optical properties. Our results also suggest a natural growth pathway of AgCu clusters through high-stability polyicosahedral structures. Results for AuCu clusters of the same size are reported for comparison, showing that the interplay of the different effects is highly material specific.     

Multifunctional chemical vapor sensors of aligned carbon nanotube and polymer composites

Partially coating perpendicularly aligned carbon nanotube arrays with an appropriate polymer thin film along their tube length provides a novel concept for developing new sensors of high sensitivity, good selectivity, and excellent environmental stability for the detection of a broad class of chemical vapors with low power consumption. The absorption and desorption of chemical vapors by the polymer matrix cause changes in the inter-tube distance and, hence, the surface resistance across the nanotube film. Simple measurements of the resistance change, therefore, constitute the nanotube-polymer chemical vapor sensors. These rationally designed, aligned carbon nanotube-polymer composite films are flexible and can be effectively integrated into many systems for a wide range of potential applications, including their use as multifunctional sensors for sensing chemical vapors, mechanical deformations, thermal and optical exposures.     

Dispersion interactions and vibrational effects in ice as a function of pressure: a first principles study

We present a first principles theoretical framework that accurately accounts for several properties of ice, over a wide pressure range. In particular, we show that, by using a recently developed nonlocal van der Waals functional and by taking into account hydrogen zero point motion, one can properly describe the zero temperature equation of state, the vibrational spectra, and the dielectric properties of ice at low pressure and of ice VIII, a stable phase between 2 and 60?GPa. While semilocal density functionals yield a transition pressure from ice XI to VIII that is overestimated by almost an order of magnitude, we find good agreement with experiments when dispersion forces are taken into account. Zero point energy contributions do not alter the computed transition pressure, but they affect structural properties, including equilibrium volumes and bulk moduli.