Condensed representations of protein secondary structure sequences and their application

In this paper, we propose a nongraphical representation for protein secondary structures. By counting the frequency of occurrence of all possible four-tuples (i.e., four-letter words) of a protein secondary structure sequence, we construct a set of 3x3 matrices for the corresponding protein secondary structure sequence. Furthermore, the leading eigenvalues of these matrices are computed and considered as invariants for the protein secondary structure sequences. To illustrate the utility of our approach, we apply it to a set of real data to distinguish protein structural classes. The result indicates that it can be used to complement the classification of protein secondary structures.     

Effects of three biological control approaches and their combination on the restoration of eutrophicated waterbodies

Choosing appropriate approaches is a key to successfully using biological control measures to accelerate the recovery of eutrophic waterbodies. In this study, we used three biomanipulation approaches—including introducing filter-feeding bivalves, stocking planktivorous fish, replanting submerged macrophytes—as well as an approach that combined all three of these methods in order to investigate their effects on water quality and plankton communities within simulation experiment systems. The experimental results showed that only stocking filter-feeding bivalves or fish could not significantly control the total algal biomass and water nutrient concentrations compared to those of the controls. The cladoceran biomasses were reduced under the treatments of stocking filter-feeding bivalves or fish. However, replanting macrophytes and a combined biological restoration approach could significantly reduce the algal biomass and the nutrient content, and both of these methods increased cladoceran biomass. The results of factor analysis of ten environmental parameters suggested that a combined biological restoration treatment was the most effective at controlling the algal biomass and reducing the nutrient content. In conclusion, combination of biological restoration measures was the best treatment out of the three treatments that were tested, and we suggest that more whole-lake scale experiments are needed. Additionally, designing a combined approach should not be a simple superposition of individual measures, but the measures should be complementary to each other.     

An empirical approach to protein conformation stability and flexibility

Experimental measurements of disulfide bond stability at various stages of protein folding are considered in terms of the effective concentrations of the thiol groups relative to each other; values of up to 10⁷M are observed, so that intramolecular interactions within the interior of a protein are much more stable, and provide greater stability to the folded conformation, than those on the surface or in a flexible segment. Intramolecular interactions can have substantially lower free energies than intermolecular, for solely entropic reasons; this implies that polar interactions, such as hydrogen bonds and salt bridges, can provide net stabilization to a folded conformation, in spite of the unfolded protein having intermolecular interactions with the solvent. These considerations can account for the lower free energy and enthalpy of the folded state and are useful for considering protein flexibility.     

Emerging computational approaches for the study of protein allostery

Allosteric regulation of protein function is key in controlling cellular processes so its underlying mechanisms are of primary concern to research in areas spanning protein engineering and drug design. However, due to the complex nature of allosteric mechanisms, a clear and predictive understanding of the relationship between protein structure and allosteric function remains elusive. Well established experimental approaches are available to offer a limited degree of characterization of mechanical properties within proteins, but the analytical capabilities of computational methods are evolving rapidly in their ability to accurately define the subtle and concerted structural dynamics that comprise allostery. This review includes a brief overview of allostery in proteins and an exploration of relevant experimental methods. An explanation of the transition from experimental toward computational methods for allostery is discussed, followed by a review of existing and emerging methods.     

Two-dimensional NMR approaches to the study of protein structure and function

Two-dimensional Fourier transform methods for homonuclear proton NMR spectroscopy have been introduced by Wüthrich and Ernst as a means of extending assignments in spectra of proteins. Multinuclear two-dimensional approaches also appear promising. We are applying current one- and two-dimensional NMR methods to protein family members that differ from one another by one or more amino acid substitutions. The overall goal is to elucidate relationships among the sequences, structures, and functions of these proteins: for example, to delineate primary structural requirements for changes in observable properties such as conformation, amino acid side chain dynamics, hydrogen exchange dynamics, pK'a values, and oxidation-reduction potentials. The ovomucoids from a variety of species of birds, which include a single set of 12 pairs of third-domain proteins (Mr = 6062 for turkey third domain, similar for others) that differ by single amino acid substitutions, provide a favorable system for the study of the structural and dynamic effects of single amino acid replacements. X-ray crystallographic structures of two ovomucoid third domains are available. Other series of proteins being studied by these methods include the photosynthetic electron transport proteins ferredoxin and plastocyanin.     

Reconciling the optimal and empirical approaches to modelling stomatal conductance

Models of vegetation function are widely used to predict the effects of climate change on carbon, water and nutrient cycles of terrestrial ecosystems, and their feedbacks to climate. Stomatal conductance, the process that governs plant water use and carbon uptake, is fundamental to such models. In this paper, we reconcile two long‐standing theories of stomatal conductance. The empirical approach, which is most commonly used in vegetation models, is phenomenological, based on experimental observations of stomatal behaviour in response to environmental conditions. The optimal approach is based on the theoretical argument that stomata should act to minimize the amount of water used per unit carbon gained. We reconcile these two approaches by showing that the theory of optimal stomatal conductance can be used to derive a model of stomatal conductance that is closely analogous to the empirical models. Consequently, we obtain a unified stomatal model which has a similar form to existing empirical models, but which now provides a theoretical interpretation for model parameter values. The key model parameter, g₁, is predicted to increase with growth temperature and with the marginal water cost of carbon gain. The new model is fitted to a range of datasets ranging from tropical to boreal trees. The parameter g₁ is shown to vary with growth temperature, as predicted, and also with plant functional type. The model is shown to correctly capture responses of stomatal conductance to changing atmospheric CO₂, and thus can be used to test for stomatal acclimation to elevated CO₂. The reconciliation of the optimal and empirical approaches to modelling stomatal conductance is important for global change biology because it provides a simple theoretical framework for analyzing, and simulating, the coupling between carbon and water cycles under environmental change.     

An empirical energy potential with a reference state for protein fold and sequence recognition.

We consider modifications of an empirical energy potential for fold and sequence recognition to represent approximately the stabilities of proteins in various environments. A potential used here includes a secondary structure potential representing short-range interactions for secondary structures of proteins, and a tertiary structure potential consisting of a long-range, pairwise contact potential and a repulsive packing potential. This potential is devised to evaluate together the total conformational energy of a protein at the coarse grained residue level. It was previously estimated from the observed frequencies of secondary structures, from contact frequencies between residues, and from the distributions of the number of residues in contact in known protein structures by regarding those distributions as the equilibrium distributions with the Boltzmann factor of these interaction energies. The stability of native structures is assumed as a primary requirement for proteins to fold into their native structures. A collapse energy is subtracted from the contact energies to remove the protein size dependence and to represent protein stabilities for monomeric and multimeric states. The free energy of the whole ensemble of protein conformations that is subtracted from the conformational energy to represent protein stability is approximated as the average energy expected for a typical native structure with the same amino acid composition. This term may be constant in fold recognition but essentially varies in sequence recognition. A simple test of threading sequences into structures without gaps is employed to demonstrate the importance of the present modifications that permit the same potential to be utilized for both fold and sequence recognition. Proteins 1999;36:357-369. Published 1999 Wiley-Liss, Inc.     

An empirical energy function for threading protein sequence through the folding motif

In this paper we present a new residue contact potantial derived by statistical analysis of protein crystal structures. This gives mean hydrophobic and pairwise contact energies as a function of residue type and distance interval. To test the accuracy of this potential we generate model structures by “threading” different sequences through backbone folding motifs found in the structural data base. We find that conformational energies calculated by summing contact potentials show perfect specificity in matching the correct sequences with each globular folding motif in a 161-protcin data set. They also identify correct models with the core folding motifs of heme-rythrin and immunoglobulin McPC603 V₁-do- main, among millions of alternatives possible when we align subsequences with α-helices and β-strands, and allow for variation in the lengths of intervening loops. We suggest that contact potentials reflect important constraints on nonbonded interaction in native proteins, and that “threading” may be useful for structure prediction by recognition of folding motif. © 1993 Wiley-Liss, Inc.     

An empirical study on the dynamic effect of regional industrial carbon transfer in China

The dynamic trend of regional industrial carbon transfer along with industrial transfers in China is currently a hot topic. To explore this problem, the gravity model has been used to study the spatial distribution of industrial transfer and industrial carbon transfer. The results indicate that both barycenters are moving westward. Based on the STIRPAT model, a system-GMM model was then constructed that introduced the industrial transfer factor and its square to explore temporal changes in regional industrial carbon transfer in the course of industrial transfer. The estimated results revealed that the relationship between industrial transfer and industrial carbon transfer displays an inverted U-shaped pattern. For every 1% increase in industrial transfer, there was a 0.327% increase in industrial carbon transfer before the turning point, but industrial carbon transfer decreased by 0.07% when it passed the “peak”. Because no province had surpassed the turning point, carbon transfer during industrial transfer in China is currently in the growth phase. Moreover, real GDP per capita, industrial structure, and industrial carbon emission intensity promoted carbon emissions reduction in the course of industrial transfer.     

Measuring fractions of beta diversity and their relationships to nestedness: a theoretical and empirical comparison of novel approaches

Beta diversity and nestedness are central concepts of ecology and biogeography and evaluation of their relationships is in the focus of contemporary ecological and conservation research. Beta diversity patterns are originated from two distinct processes: the replacement (or turnover) of species and the loss (or gain) of species leading to richness differences. Nested distributional patterns are generally thought to have a component deriving from beta diversity which is independent of replacement processes. Quantification of these phenomena is often made by calculating a measure of beta diversity, and the resulting value being subsequently partitioned into a contribution by species replacement plus a fraction shared by beta diversity and nestedness. Three methods have been recently proposed for such partitioning, all of them based on pairwise comparisons of sites. In this paper, the performance of these methods was evaluated on theoretical grounds and tested by a simulation study in which different gradients of dissimilarity, with known degrees of species replacement and species loss, were created. Performance was also tested using empirical data addressing land‐use induced changes in endemic arthropod communities of the Terceira Island in the Azores. We found that the partitioning of β_cc (dissimilarity in terms of the Jaccard index) into two additive fractions, β_‐3 (dissimilarity due to species replacement) plus β_rich (dissimilarity due to richness differences) reflects the species replacement and species loss processes across the simulated gradients in an ecologically and mathematically meaningful way, whilst the other two methods lack mathematical consistency and prove conceptually self‐contradictory. Moreover, the first method identified a selective local extinction process for endemic arthropods, triggered by land‐use changes, while the latter two methods overweighted the replacement component and led to false conclusions. Their basic flaw derives from the fact that the proposed replacement and nestedness components (deemed to account for species loss) are not scaled in the same way as the measure that accounts for the total dissimilarity (Sørensen and Jaccard indices). We therefore recommend the use of β_cc=β_‐3+β_rich, since its components are scaled in the same units and their responses are proportional to the replacement and the gain/loss of species.     

Animal rights activists' representations of animals and animal rights: An exploratory study

Abstract

During the last 30 years, supporters of the animal rights movement have questioned the use of animals for human benefit and have campaigned for improvements in their welfare. In the present study, activists' representations of animals and animal rights were investigated by interviewing 23 participants (from three animal welfare and animal rights organizations) during four focus-group discussions. Results show that the activists' representations were generated from the love/pain thema, which on the one hand showed the compassion and love the activists have for animals, and on the other hand the suffering that animals can endure. Moreover, differences were found in this study in the way that members of the three animal welfare and rights organizations constructed their views of animals. While members of two out of the three organizations aimed to protect abandoned animals, members of the Anti-Vivisection League faced the contradictions within the human–animal relationship and endorsed a more coherent approach to animals. These findings are interpreted in light of previous studies conducted on the animal rights movement and of recent developments in social representation theory.     

Global profiling of protein complexes: current approaches and their perspective in biomedical research

Introduction: Despite the rapid evolution of proteomic methods, protein interactions and their participation in protein complexes – an important aspect of their function – has rarely been investigated on the proteome-wide level. Disease states, such as muscular dystrophy or viral infection, are induced by interference in protein-protein interactions within complexes. The purpose of this review is to describe the current methods for global complexome analysis and to critically discuss the challenges and opportunities for the application of these methods in biomedical research.

Areas covered: We discuss advancements in experimental techniques and computational tools that facilitate profiling of the complexome. The main focus is on the separation of native protein complexes via size exclusion chromatography and gel electrophoresis, which has recently been combined with quantitative mass spectrometry, for a global protein-complex profiling. The development of this approach has been supported by advanced bioinformatics strategies and fast and sensitive mass spectrometers that have allowed the analysis of whole cell lysates. The application of this technique to biomedical research is assessed, and future directions are anticipated.

Expert commentary: The methodology is quite new, and has already shown great potential when combined with complementary methods for detection of protein complexes.     

Comparison of sequence-based and structure-based phylogenetic trees of homologous proteins: Inferences on protein evolution

Several studies based on the known three-dimensional (3-D) structures of proteins show that two homologous proteins with insignificant sequence similarity could adopt a common fold and may perform same or similar biochemical functions. Hence, it is appropriate to use similarities in 3-D structure of proteins rather than the amino acid sequence similarities in modelling evolution of distantly related proteins. Here we present an assessment of using 3-D structures in modelling evolution of homologous proteins. Using a dataset of 108 protein domain families of known structures with at least 10 members per family we present a comparison of extent of structural and sequence dissimilarities among pairs of proteins which are inputs into the construction of phylogenetic trees. We find that correlation between the structure-based dissimilarity measures and the sequence-based dissimilarity measures is usually good if the sequence similarity among the homologues is about 30% or more. For protein families with low sequence similarity among the members, the correlation coefficient between the sequence-based and the structure-based dissimilarities are poor. In these cases the structure-based dendrogram clusters proteins with most similar biochemical functional properties better than the sequence-similarity based dendrogram. In multi-domain protein families and disulphide-rich protein families the correlation coefficient for the match of sequence-based and structure-based dissimilarity (SDM) measures can be poor though the sequence identity could be higher than 30%. Hence it is suggested that protein evolution is best modelled using 3-D structures if the sequence similarities (SSM) of the homologues are very low.     

An empirical study of the evolution of virulence under both horizontal and vertical transmission

According to current thinking, a parasite's transmission mode will be a major determinant of virulence, defined as the harm induced by parasites to their hosts. With horizontal transmission, virulence will increase as a byproduct of a trade-off between fitness gained through increased among-host transmission (infectivity) and fitness lost through increased virulence. With vertical transmission, virulence will decrease because a parasite's reproductive potential will be maximized only by decreasing harm to the host, allowing parasite transmission to more host offspring. To test both predictions, we transmitted barley stripe mosaic virus (BSMV) horizontally and then vertically in its host, barley (Hordeum vulgare). After four generations of horizontal transmission, we observed a nearly twofold increase in horizontal infectivity and nearly tripled virulence. After three generations of subsequent vertical transmission, we observed a modest (16%) increase in vertical transmissibility and a large (40%) reduction in virulence. Increased horizontal transmission is often due to increased pathogen replication which, in turn, causes increased virulence. However, we found no correlation between within-host virus concentration and virulence, indicating that the observed changes in virulence were not due to changes in viral titer. Finally, horizontally transmitted BSMV had reduced vertical transmission and vertically transmitted BSMV had reduced horizontal infectivity. These two observations suggest that, in nature, in different host populations with varying opportunities for horizontal and vertical transmission, different viral strains may be favored.