On the influence of point defects on the structural and electronic properties of graphene-like sheets: a molecular simulation study

The influence of vacancies and substitutional defects on the structural and electronic properties of graphene, graphene oxide, hexagonal boron nitride, and boron nitride oxide two-dimensional molecular models was studied using density functional theory (DFT) at the level of local density approximation (LDA). Bond length, dipole moment, HOMO–LUMO energy gap, and binding energy were calculated for each system with and without point defects. The results obtained indicate that the formation of a point defect does not necessary lead to structural instability; nevertheless, surface distortions and reconstruction processes were observed, mainly when a vacancy-type defect is generated. For graphene, it was found that incorporation of a point defect results in a semiconductor–semimetal transition and also increases notably its polar character. As with graphene, the formation of a point defect in a hexagonal boron nitride sheet reduces its energy gap, although its influence on the resulting dipole moment is not as dramatic as in graphene. The influence of point defects on the structural and electronic properties of graphene oxide and boron nitride oxide sheets were found to be mediated by the chemisorbed species.     

ETS-NOCV decomposition of the reaction force for double-proton transfer in formamide-derived systems

The analysis of the electronic-structure changes along IRC paths for double-proton-transfer reactions in the formamide dimer (R1), formamide–thioformamide system (R2), and the thioformamide dimer (R3) was performed based on the extended-transition-state natural orbitals for chemical valence (ETS-NOCV) partitioning of the reaction force, considering the intra-fragments strain and the inter-fragments interaction terms, and further—the electrostatic, Pauli-repulsion and orbital interaction components, with the latter being decomposed into the NOCV components. Two methods of the system partitioning into the fragments were considered (‘reactant perspective’/bond-formation, ‘product perspective’ / bond-breaking). In agreement with previous studies, the results indicate that the major changes in the electronic structure occur in the transition state region; the bond-breaking processes are, however, initiated already in the reactant region, prior to entering the TS region. The electrostatic contributions were identified as the main factor responsible for the increase in the activation barrier in the order R1?<?R2?<?R3.     

Parasite-mediated and direct competition in a two-host shared macroparasite system

This paper investigates the local dynamical behaviour of a deterministic model describing two host species experiencing three forms of competition: direct competition, apparent competition mediated by macroparasites, and intra-specific (density-dependent) competition. The problem of algebraic intractability is sidestepped by adopting a geometric approach, in which an array of maps is constructed in parameter space, each structured by bifurcation surfaces which mark qualitative changes in system behaviour. The maps provide both a succinct and a comprehensive overview of the stability and feasibility structure of the system equilibria, from which can be deduced the possible modes of local dynamical behaviour. A detailed examination of these maps shows that (i) the system is highly sensitive to the effect of infection on fecundity with synchronous sustained cycles readily generated by Hopf bifurcations; (ii) for a broad range of parameter values, pertinent to actual biological systems, apparent competition mediated by macroparasites is sufficient, on its own, to explain host exclusion; (iii) direct competition reinforces parasite-mediated competition to expand the host exclusion region; and (iv) the condition for host exclusion can be expressed simply in a form which holds for both micro- and macroparasite models and which involves just two key indices, measuring tolerance to the infection and the strength of direct competition. The techniques used in this paper are not restricted to the analysis of host-parasite systems but can be applied to a wide range of nonlinear population models. They are therefore as relevant to the analysis of such general issues as exploitative competition and trophic interactions as they are to specific epidemiological problems.     

Local interactions and the optimization of protein folding

The role of local interactions in protein folding has recently been the subject of some controversy. Here we investigate an extension of Zwanzig's simple and general model of folding in which local and nonlocal interactions are represented by functions of single and multiple conformational degrees of freedom, respectively. The kinetics and thermodynamics of folding are studied for a series of energy functions in which the energy of the native structure is fixed, but the relative contributions of local and nonlocal interactions to this energy are varied over a broad range. For funnel shaped energy landscapes, we find that 1) the rate of folding increases, but the stability of the folded state decreases, as the contribution of local interactions to the energy of the native structure increases, and 2) the amount of native structure in the unfolded state and the transition state vary considerably with the local interaction strength. Simple exponential kinetics and a well-defined free energy barrier separating folded and unfolded states are observed when nonlocal interactions make an appreciable contribution to the energy of the native structure; in such cases a transition state theory type approximation yields reasonably accurate estimates of the folding rate. Bumps in the folding funnel near the native state, which could result from desolvation effects, side chain freezing, or the breaking of nonnative contacts, significantly alter the dependence of the folding rate on the local interaction strength: the rate of folding decreases when the local interaction strength is increased beyond a certain point. A survey of the distribution of strong contacts in the protein structure database suggests that evolutionary optimization has involved both kinetics and thermodynamics: strong contacts are enriched at both very short and very long sequence separations. Proteins 29:282–291, 1997. © 1997 Wiley-Liss, Inc.     

Discrimination of near-native structures in protein-protein docking by testing the stability of local minima

Fast Fourier transform (FFT) correlation methods of protein-protein docking, combined with the clustering of low energy conformations, can find a number of local minima on the energy surface. For most complexes, the locations of the near-native structures can be constrained to the 30 largest clusters, each surrounding a local minimum. However, no reliable further discrimination can be obtained by energy measures because the differences in the energy levels between the minima are comparable with the errors in the energy evaluation. In fact, no current scoring function accounts for the entropic contributions that relate to the width rather than the depth of the minima. Since structures at narrow minima loose more entropy, some of the nonnative states can be detected by determining whether or not a local minimum is surrounded by a broad region of attraction on the energy surface. The analysis is based on starting Monte Carlo Minimization (MCM) runs from random points around each minimum, and observing whether a certain fraction of trajectories converge to a small region within the cluster. The cluster is considered stable if such a strong attractor exists, has at least 10 convergent trajectories, is relatively close to the original cluster center, and contains a low energy structure. We studied the stability of clusters for enzyme-inhibitor and antibody-antigen complexes in the Protein Docking Benchmark. The analysis yields three main results. First, all clusters that are close to the native structure are stable. Second, restricting considerations to stable clusters eliminates around half of the false positives, that is, solutions that are low in energy but far from the native structure of the complex. Third, dividing the conformational space into clusters and determining the stability of each cluster, the combined approach is less dependent on a priori information than exploring the potential conformational space by Monte Carlo minimizations.     

Stability switches,oscillatory multistability,and spatio-temporal patterns of nonlinear oscillations in recurrently delay coupled neural networks

A model of time-delay recurrently coupled spatially segregated neural assemblies is here proposed. We show that it operates like some of the hierarchical architectures of the brain. Each assembly is a neural network with no delay in the local couplings between the units. The delay appears in the long range feedforward and feedback inter-assemblies communications. Bifurcation analysis of a simple four-units system in the autonomous case shows the richness of the dynamical behaviors in a biophysically plausible parameter region. We find oscillatory multistability, hysteresis, and stability switches of the rest state provoked by the time delay. Then we investigate the spatio-temporal patterns of bifurcating periodic solutions by using the symmetric local Hopf bifurcation theory of delay differential equations and derive the equation describing the flow on the center manifold that enables us determining the direction of Hopf bifurcations and stability of the bifurcating periodic orbits. We also discuss computational properties of the system due to the delay when an external drive of the network mimicks external sensory input.     

The structural characterization and antigenicity of the S protein of SARS-CoV

The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and posit     

Energy landscape and dynamics of the beta-hairpin G peptide and its isomers: Topology and sequences

We have investigated free energy landscape [MM/PBSA + normal modes entropy] of permutations in the G peptide (41-56) from the protein G B1 domain by studying six isomers corresponding to moving the hydrophobic cluster along the beta-strands (toward the turn: T1, AGEWTYDDKTFTVTET; T2, GEDTWDYATFTVTKTE; T3, GEDDWTYATFTVTKTE; toward the end: E1, WTYDDAGETKTFTVT; E2, WEYTGDDATKTETFTV; E3, WTYEGDDATKTETFTV). The free energy terms include molecular mechanics energy, Poisson-Boltzmann electrostatic solvation energy, surface area solvation energy, and conformational entropy estimated by using normal mode analysis. From the wild type to T1, then T3, and finally T2, we see a progressively changing energy landscape, toward a less stable beta-hairpin structure. Moving the hydrophobic cluster outside toward the end region causes a greater change in the energy landscape. alpha-Helical instead of a beta-hairpin structure was the most stable form for the E2 isomer. However, no matter how much the sequence changes, for all variants studied, ideal "native" beta-hairpin topologies remain as minima (regardless of whether global or local) in the energy landscape. In general, we find that the energy landscape is dependent on the hydrophobic cluster topology and on the sequence. Our present study indicates that the key is the relative conformational energies of the different conformations. Changes in the sequence strongly modulate the relative stabilities of topologically similar regions in the energy landscape, rather than redefine the topology space. This finding is consistent with a population redistribution in the process of protein folding. The limited variation of topological space, compared with the number of possible sequence changes, may relate to the observation that the number of known protein folds are far less than the sequential allowance.     

Novel cloning method for recombinant adenovirus construction in Escherichia coli

pAd(vantage) is a rapid cloning system for generating recombinant adenoviruses. The system is based on manipulating the full-length adenovirus genome as a stable plasmid in E. coli using intron-encoded endonucleases. These intron-encoded endonucleases cut their recognition sequences, which range from 15-39 bp, with high specificity. Their unusual long homing sequence makes them rare-cutting and ideal for use as cloning sites. We report how transgenes can easily be cloned directly into the E1 region of an adenoviral plasmid, followed by transfection into a mammalian packaging cell line, to produce homogeneous recombinant viruses without the need for plaque purification.     

Protein structure refinement based on paramagnetic NMR shifts: applications to wild-type and mutant forms of cytochrome c.

A new approach to NMR solution structure refinement is introduced that uses paramagnetic effects on nuclear chemical shifts as constraints in energy minimization or molecular dynamics calculations. Chemical shift differences between oxidized and reduced forms of horse cytochrome c for more than 300 protons were used as constraints to refine the structure of the wild-type protein in solution and to define the structural changes induced by a Leu 94 to Val mutation. A single round of constrained minimization, using the crystal structure as the starting point, converged to a low-energy structure with an RMS deviation between calculated and observed pseudo-contact shifts of 0.045 ppm, 7.5-fold lower than the starting structure. At the same time, the procedure provided stereospecific assignments for more than 45 pairs of methylene protons and methyl groups. Structural changes caused by the mutation were determined to a precision of better than 0.3 A. Structure determination based on dipolar paramagnetic (pseudocontact) shifts is applicable to molecules containing anisotropic paramagnetic centers with short electronic relaxation times, including numerous naturally occurring metalloproteins, as well as proteins or nucleic acids to which a paramagnetic metal ion or ligand may be attached. The long range of paramagnetic shift effects (up to 20 A from the iron in the case of cytochrome c) provides global structural constraints, which, in conjunction with conventional NMR distance and dihedral angle constraints, will enhance the precision of NMR solution structure determination.     

The Free Energy Barrier for Arginine Gating Charge Translation Is Altered by Mutations in the Voltage Sensor Domain

The gating of voltage-gated ion channels is controlled by the arginine-rich S4 helix of the voltage-sensor domain moving in response to an external potential. Recent studies have suggested that S4 moves in three to four steps to open the conducting pore, thus visiting several intermediate conformations during gating. However, the exact conformational changes are not known in detail. For instance, it has been suggested that there is a local rotation in the helix corresponding to short segments of a 3-helix moving along S4 during opening and closing. Here, we have explored the energetics of the transition between the fully open state (based on the X-ray structure) and the first intermediate state towards channel closing (C), modeled from experimental constraints. We show that conformations within 3 Å of the X-ray structure are obtained in simulations starting from the C model, and directly observe the previously suggested sliding 3-helix region in S4. Through systematic free energy calculations, we show that the C state is a stable intermediate conformation and determine free energy profiles for moving between the states without constraints. Mutations indicate several residues in a narrow hydrophobic band in the voltage sensor contribute to the barrier between the open and C states, with F233 in the S2 helix having the largest influence. Substitution for smaller amino acids reduces the transition cost, while introduction of a larger ring increases it, largely confirming experimental activation shift results. There is a systematic correlation between the local aromatic ring rotation, the arginine barrier crossing, and the corresponding relative free energy. In particular, it appears to be more advantageous for the F233 side chain to rotate towards the extracellular side when arginines cross the hydrophobic region.     

Engineering Local Coordination Environments of Atomically Dispersed and Heteroatom‐Coordinated Single Metal Site Electrocatalysts for Clean Energy‐Conversion

Carbon‐based heteroatom‐coordinated single‐atom catalysts (SACs) are promising candidates for energy‐related electrocatalysts because of their low‐cost, tunable catalytic activity/selectivity, and relatively homogeneous morphologies. Unique interactions between single metal sites and their surrounding coordination environments play a significant role in modulating the electronic structure of the metal centers, leading to unusual scaling relationships, new reaction mechanisms, and improved catalytic performance. This review summarizes recent advancements in engineering of the local coordination environment of SACs for improved electrocatalytic performance for several crucial energy‐convention electrochemical reactions: oxygen reduction reaction, hydrogen evolution reaction, oxygen evolution reaction, CO₂ reduction reaction, and nitrogen reduction reaction. Various engineering strategies including heteroatom‐doping, changing the location of SACs on their support, introducing external ligands, and constructing dual metal sites are comprehensively discussed. The controllable synthetic methods and the activity enhancement mechanism of state‐of‐the‐art SACs are also highlighted. Recent achievements in the electronic modification of SACs will provide an understanding of the structure–activity relationship for the rational design of advanced electrocatalysts.     

Deletion of the gene encoding the adenovirus 5 early region 1b 21,000-molecular-weight polypeptide leads to degradation of viral and host cell DNA.

The adenovirus 5 mutant H5dl337 lacks 146 base pairs within early region 1B. The deletion removes a portion of the region encoding the E1B 21,000-molecular-weight (21K) polypeptide, but does not disturb the E1B-55K/17K coding region. The virus is slightly defective for growth in cultured HeLa cells, in which its final yield is reduced ca. 10-fold compared with wild-type virus. The mutant displays a striking phenotype in HeLa cells. The onset of cytopathic effect is dramatically accelerated, and both host cell and viral DNAs are extensively degraded late after infection. This defect has been described previously for a variety of adenovirus mutants and has been termed a cytocidal (cyt) phenotype. H5dl337 serves to map this defect to the loss of E1B-21K polypeptide function. In addition to its defect in the productive growth cycle, H5dl337 is unable to transform rat cells at normal efficiency.     

Functional characterization of thermolabile DNA-binding proteins that affect adenovirus DNA replication.

The human adenovirus type 2 (Ad2) mutant Ad2ts111 has previously been shown to contain two mutations which result in a complex phenotype. Ad2ts111 contains a single base change in the early region 1B (E1B) 19,000-molecular-weight (19K) coding region which yields a cyt deg phenotype and another defect which maps to the E2A 72K DNA-binding protein (DBP) coding region that causes a temperature-sensitive DNA replication phenotype. Here we report that the defect in the Ad2ts111 DBP is due to a single G----T transversion that results in a substitution of valine for glycine at amino acid 280. A temperature-independent revertant, Ad2ts111R10, was isolated, which reverts back to glycine at amino acid 280 yet retains the cyt and deg phenotypes caused by the 19K mutation. We physically separated the two mutations of Ad2ts111 by constructing a recombinant virus, Ad2ts111A, which contained a wild-type Ad2 E1B 19K gene and the gly----val mutation in the 72K gene. Ad2ts111A was cyt+ deg+, yet it was still defective for DNA replication at the nonpermissive temperature. The Ad2ts111 DBP mutation is located only two amino acids away from the site of the mutation in Ad2+ND1ts23, a previously sequenced DBP mutant. Biochemical studies of purified Ad2+ND1ts23 DBP showed that this protein was defective for elongation but not initiation of replication in a cell-free replication system consisting of purified Ad polymerase, terminal protein precursor, and nuclear factor I. Ad2+ND1ts23 DBP bound less tightly to single-strand DNA than did Ad2 DBP, as shown by salt gradient elution of purified DBPs from denatured DNA cellulose columns. This decreased binding to DNA was probably due to local conformational changes in the protein at a site that is critical for DNA binding rather than to global changes in protein structure, since both the Ad2+ND1ts23 and Ad2 DBPs showed identical cleavage patterns by the protease thermolysin at various temperatures.     

Complete Demonstration of the Valence Electronic Structure Inside a Practical Organic Solar Cell Probed by Low Energy Photoemission

The complete electronic structure inside a practical organic photovoltaic (OPV) device consisting of a trilayer structure of copper‐phthalocyanine (CuPc), fullerene (C₆₀), and bathocuproine (BCP) is demonstrated using low‐energy ultraviolet photoelectron spectroscopy (LE‐UPS) and photoelectron yield spectroscopy (PYS). The molecular orbital energy alignment and electrostatic potential distribution throughout the entire device is illustrated based on the LE‐UPS results. A favorable potential gradient to carry the photogenerated holes and electrons is manifested to be built spontaneously in the CuPc and BCP layers, respectively. Furthermore, the ultrahigh sensitivity measurements of LE‐UPS clearly unveil the distributions of faint density‐of‐states in the energy‐gap region in the organic films. Substantially barrierless contacts to both electrodes are fulfilled by the existence of these gap states. The electronic structure under simulated sunlight illumination is examined for the purpose of elucidating the electronic structures inside the working devices in the open‐circuit condition. These results indicate experimentally the electronic functionalities of each organic material, in particular of the BCP buffer layer, on the cell efficiency.     

Effects of Voltage Biasing on Current Extraction in Perovskite Solar Cells

The recent rapid increase in efficiency of organic–inorganic perovskite solar cells (PSCs) has resulted in a need to develop a clear understanding of their stability and working mechanisms. In particular, it has been suggested that ion migration contributes to the commonly observed hysteresis in the current–voltage measurements of PSCs, but the rate of ion migration and its effects on the electronic properties of PSCs remain to be addressed. In this work, electron‐beam‐induced current (EBIC) is used to directly map changes in local current extraction in organic–inorganic PSCs under applied voltage. By combining EBIC mapping, standard current–voltage measurements, and external quantum efficiency measurements, it is shown that between the two potential roles that point defects play in device enhancement under voltage biasing, the effects caused by defect‐mediated ion migration outweigh the effects from the filling of trap states caused by these defects. Evidence is also provided for ion migration preferentially at local features such as extended defects. The measured timescale of tens of seconds for migration across a full device imply that ion migration contributes indirectly to the electronic capacitance of perovskite devices through interface charging.     

Sensing site‐specific structural characteristics and chirality using vibrational circular dichroism of isotope labeled peptides

Isotope labeling has a long history in chemistry as a tool for probing structure, offering enhanced sensitivity, or enabling site selection with a wide range of spectroscopic tools. Chirality sensitive methods such as electronic circular dichroism are global structural tools and have intrinsically low resolution. Consequently, they are generally insensitive to modifications to enhance site selectivity. The use of isotope labeling to modify vibrational spectra with unique resolvable frequency shifts can provide useful site‐specific sensitivity, and these methods have been recently more widely expanded in biopolymer studies. While the spectral shifts resulting from changes in isotopic mass can provide resolution of modes from specific parts of the molecule and can allow detection of local change in structure with perturbation, these shifts alone do not directly indicate structure or chirality. With vibrational circular dichroism (VCD), the shifted bands and their resultant sign patterns can be used to indicate local conformations in labeled biopolymers, particularly if multiple labels are used and if their coupling is theoretically modeled. This mini‐review discusses selected examples of the use of labeling specific amides in peptides to develop local structural insight with VCD spectra.     

Relative fitness of a generalist parasite on two alternative hosts: a cross‐infestation experiment to test host specialization of the hen flea Ceratophyllus gallinae (Schrank)

Host range is a key element of a parasite's ecology and evolution and can vary greatly depending on spatial scale. Generalist parasites frequently show local population structure in relation to alternative sympatric hosts (i.e. host races) and may thus be specialists at local scales. Here, we investigated local population specialization of a common avian nest‐based parasite, the hen flea Ceratophyllus gallinae (Schrank), exploiting two abundant host species that share the same breeding sites, the great tit Parus major (Linnaeus) and the collared flycatcher Ficedula albicollis (Temminck). We performed a cross‐infestation experiment of fleas between the two host species in two distinct study areas during a single breeding season and recorded the reproductive success of both hosts and parasites. In the following year, hosts were monitored again to assess the long‐term impact of cross‐infestation. Our results partly support the local specialization hypothesis: in great tit nests, tit fleas caused higher damage to their hosts than flycatcher fleas, and in collared flycatcher nests, flycatcher fleas had a faster larval development rates than tit fleas. However, these results were significant in only one of the two studied areas, suggesting that the location and history of the host population can modulate the specialization process. Caution is therefore called for when interpreting single location studies. More generally, our results emphasize the need to explicitly account for host diversity in order to understand the population ecology and evolutionary trajectory of generalist parasites.