Estimation of important binding sites in compounds that interact with proteins

Proteins are one of the important substances in understanding biological activity, and many of them express the function by binding to other proteins or small molecules (ligands) on the molecular surface. This interaction often occurs in the hollows (pockets) on the molecular surface of the protein. It is known that when pockets are similar in structure and physical properties, they are likely to express similar functions and to bind similar ligands. Therefore, exploring the similarity of the structure and physical properties in pockets is very useful because it leads to the discovery of new ligands that are likely to bind. In addition, exploring the important structure when binding to the protein significant spot in the ligand will provide useful knowledge for the development of new ligands.In this study, we propose a method to search for proteins containing pockets that are structurally and physically similar to significant spot in the pocket of the analyzed protein, and to extract significant spots in the ligands that bind to them. We use feature points as data. Feature points are the 3-dimensional points that are extracted from 3D structure data of proteins with feature values quantifying hydrophobicity and electrostatic potential. The corresponding feature points are extracted by comparing structurally and physically the pockets of the search target proteins with the significant spot of the analyzed protein. By evaluating the similarity based on the comparison results of the feature values given to the extracted feature points, we search for proteins that are similar to the analyzed protein. From the ligands that bind to the searched proteins, atoms that are near the protein pocket and similar to the atoms in ligand binding to the analyzed protein are extracted. The site constituted by the extracted atoms is defined as a significant spot in the ligand.As a result of classifying ligands binding to the protein by using the extracted significant spot in the ligand, the effectiveness of the proposed method was confirmed.     

Functionalizing inorganic solids: towards organic-inorganic nanostructured materials for intelligent and bioinspired systems

The design, preparation, and properties of organic-inorganic hybrid compounds are described and discussed with respect to their potential uses as intelligent and bioinspired materials. Several synthesis strategies based on intercalation in 2D solids, the grafting of organic groups onto silica and silicates, and the self-assembly of organo-silica materials are presented, focusing on the soft procedures that are used to modify the functionality of the inorganic substrates. The combination of both organic and inorganic moieties at the nanometer level forms the basis for preparing multifunctional solids that are provided with specific functions in response to different types of stimuli. In some cases these resemble materials that are found in biological systems. Examples include organic-inorganic membranes that are based on intercalated macrocyclic compounds and bi-layer vesicles that consist of alkyl long-chains arranged either in the confined region of layered silicates or as self-organized organo-silica micelles. The role of certain hybrid materials such as membranes provides a different approach to the development of artificial liposomes and other mimetic systems that have an organic-inorganic composition and nanostructural organization. Their potential uses for DDS or DNA-dense phases are also discussed and novel alternatives to bioinspired systems development are proposed.     

Ocular Delivery of Polyphenols: Meeting the Unmet Needs

Nature has become one of the main sources of exploration for researchers that search for new potential molecules to be used in therapy. Polyphenols are emerging as a class of compounds that have attracted the attention of pharmaceutical and biomedical scientists. Thanks to their structural peculiarities, polyphenolic compounds are characterized as good scavengers of free radical species. This, among other medicinal effects, permits them to interfere with different molecular pathways that are involved in the inflammatory process. Unfortunately, many compounds of this class possess low solubility in aqueous solvents and low stability. Ocular pathologies are spread worldwide. It is estimated that every individual at least once in their lifetime experiences some kind of eye disorder. Oxidative stress or inflammatory processes are the basic etiological mechanisms of many ocular pathologies. A variety of polyphenolic compounds have been proved to be efficient in suppressing some of the indicators of these pathologies in in vitro and in vivo models. Further application of polyphenolic compounds in ocular therapy lacks an adequate formulation approach. Therefore, more emphasis should be put in advanced delivery strategies that will overcome the limits of the delivery site as well as the ones related to the polyphenols in use. This review analyzes different drug delivery strategies that are employed for the formulation of polyphenolic compounds when used to treat ocular pathologies related to oxidative stress and inflammation.     

The Compositional Aspects of Edible Flowers as an Emerging Horticultural Product

Edible flowers are becoming very popular, as consumers are seeking healthier and more attractive food products that can improve their diet aesthetics and diversify their dietary sources of micronutrients. The great variety of flowers that can be eaten is also associated with high variability in chemical composition, especially in bioactive compounds content that may significantly contribute to human health. The advanced analytical techniques allowed us to reveal the chemical composition of edible flowers and identify new compounds and effects that were not known until recently. Considering the numerous species of edible flowers, the present review aims to categorize the various species depending on their chemical composition and also to present the main groups of compounds that are usually present in the species that are most commonly used for culinary purposes. Moreover, special attention is given to those species that contain potentially toxic or poisonous compounds as their integration in human diets should be carefully considered. In conclusion, the present review provides useful information regarding the chemical composition and the main groups of chemical compounds that are present in the flowers of the most common species.     

Are metals made from molecules?

In the traditional view, covalently bound materials differ in a fundamental way from metallic substances. Though both are built from more basic units that are, in turn, constructed from a small number of atoms, for these two materials classes the nature of these units is thought to be quite different. For covalent solids and liquids, these units are considered to be molecular, meaning that they possess properties and bonding that are retained in the condensed phase and thus they continue to be identifiable within the larger system. For metallic materials, these basic units are considered to be mere constructs that are not observable against the delocalized bonding of metals or alloys. The perceived dissimilarity of metallic and covalently bound materials has fostered distinctly different approaches to their design and improvement. Here, the delocalized view of metallic bonding is examined. This examination suggests that much of the rationale used in the design of molecular materials my be applied to metals and alloys as well.     

Hydrophobins: Proteins that self assemble at interfaces

Hydrophobins are surface active proteins that are produced by filamentous fungi. They are interesting from a Surf Sci point of view because some of their properties as surface active proteins are quite spectacular. In this review, recent advances in understanding these properties will be surveyed. We will attempt to define what the properties are that make them unique. As an understanding of both structure and function of hydrophobins is emerging we see that this is paving the way for industrial applications as well as an understanding of their biological functions.

Major recent advances

Recently there has been a clear increase in attempts to use hydrophobins in applications. We are starting to understand their unique properties as surfactants and especially applications related to the stability and development of foams and various surface treatments are emerging. There are several new reports on molecular structures as well on mechanisms of self-assembly. Hydrophobins have functions in biology that are far from understood, but also here techniques are developing and a broader understanding is emerging.     

Anti-Fungal Hevein-like Peptides Biosynthesized from Quinoa Cleavable Hololectins

Chitin-binding hevein-like peptides (CB-HLPs) belong to a family of cysteine-rich peptides that play important roles in plant stress and defense mechanisms. CB-HLPs are ribosomally synthesized peptides that are known to be bioprocessed from the following two types of three-domain CB-HLP precursor architectures: cargo-carrying and non-cargo-carrying. Here, we report the identification and characterization of chenotides biosynthesized from the third type of precursors, which are cleavable hololectins of the quinoa (Chenopodium quinoa) family. Chenotides are 6-Cys-CB-HLPs of 29–31 amino acids, which have a third type of precursor architecture that encompasses a canonical chitin-binding domain that is involved in chitin binding and anti-fungal activities. Microbroth dilution assays and microscopic analyses showed that chenotides are effective against phyto-pathogenic fungi in the micromolar range. Structure determination revealed that chenotides are cystine knotted and highly compact, which could confer resistance against heat and proteolytic degradation. Importantly, chenotides are connected by a novel 18-residue Gly/Ala-rich linker that is a target for bioprocessing by cathepsin-like endopeptidases. Taken together, our findings reveal that chenotides are a new family of CB-HLPs from quinoa that are synthesized as a single multi-modular unit and bioprocessed to yield individual mature CB-HLPs. Importantly, such precursors constitute a new family of cleavable hololectins. This unusual feature could increase the biosynthetic efficiency of anti-fungal CB-HLPs, to provide an evolutionary advantage for plant survival and reproduction.     

Three- and two-dimensional effects in wetting kinetics

Wetting at equilibrium is reviewed in brief, and it is then suggested that a wider class of nonequilibrium problems can exist where an equilibrium-like behaviour is reached simply because the mechanisms for spreading are suppressed.The mechanisms of spreading are reviewed to suggest that experiments of wetting kinetics of liquids with varying volatilities on mica would lead to interesting results. Such experiments were conducted and the results are supportive of the models. It was also observed that when volatility and surface roughness, two important mechanisms of spreading, are removed, the drop motion presumed to be controlled by surface diffusion at the contact line virtually ceases, although scanning electron microscopy results show that they are indeed moving.The role of films of ultra-low thicknesses are examined. It is seen that the dynamics of molecular scale droplets are understandable, and can be modelled in many ways, and the features these moving molecular scale drops exhibit can in some cases affect the movement of microscale drops as well.We are able to identify and define two- and three-dimensional volatilities and mobilities that help one to classify the spreading phenomena, as far as the liquids are concerned. The surfaces can be smooth or rough, a difference that has a strong effect.     

Engineering antimicrobial surfaces by harnessing polymeric nanoassemblies

The increasing number of multidrug-resistant bacteria is a growing threat to global public health. Contaminated surfaces pose a major problem in the spreading of these superbugs and are a source of bacterial infections that are difficult to treat. Surfaces that repel bacteria or impede biofilms where bacteria are inaccessible to conventional drugs are in great demand for medical and technological applications. Immense multi-disciplinary efforts are being made to develop biocompatible, long-lasting, scalable, and cost-effective antimicrobial surfaces. Here, we highlight emerging strategies that involve harnessing natural and synthetic polymeric nanoassemblies that are antimicrobial either by themselves or through association with antimicrobial compounds to engineer antimicrobial surfaces. Our aim is to move underexplored nanoassemblies into the limelight. Based on their chemical versatility, structural tenability, and orthogonal activity of associated molecules and structures, the nanoassemblies discussed overcome cytotoxicity, non-biodegradability, and short-term antibacterial activity to offer novel surfaces with improved antibacterial and antibiofilm prospects.     

Dynamics of hemoglobin in human erythrocytes and in solution: influence of viscosity studied by ultrafast vibrational echo experiments

Ultrafast spectrally resolved stimulated vibrational echo experiments are used to measure the vibrational dephasing of the CO stretching mode of hemoglobin-CO (HbCO) inside living human erythrocytes (red blood cells), in liquid solutions, and in a glassy matrix. A method is presented to overcome the adverse impact on the vibrational echo signal from the strong light scattering caused by the cells. The results from the cytoplasmic HbCO are compared to experiments on aqueous HbCO samples prepared in different buffers, solutions containing low and high concentrations of glycerol, and in a solid trehalose matrix. Measurements are also presented that provide an accurate determination of the viscosity at the very high Hb concentration that is found inside the cells. It is demonstrated that the dynamics of the protein, as sensed by the CO ligand, are the same inside the erythrocytes and in aqueous solution and are independent of the viscosity. In solutions that are predominantly glycerol, the dynamics are modified somewhat but are still independent of viscosity. The experiments in trehalose give the dynamics at infinite viscosity and are used to separate the viscosity-dependent dynamics from the viscosity-independent dynamics. Although the HbCO dynamics are the same in the red blood cell and in the equivalent aqueous solutions, differences in the absorption spectra show that the distribution of a protein's equilibrium substates is sensitive to small pH differences.     

A multidimensional discrete variable representation basis obtained by simultaneous diagonalization

Direct product basis functions are frequently used in quantum dynamics calculations, but they are poor in the sense that many such functions are required to converge a spectrum, compute a rate constant, etc. Much better, contracted, basis functions, that account for coupling between coordinates, can be obtained by diagonalizing reduced dimension Hamiltonians. If a direct product basis is used, it is advantageous to use discrete variable representation (DVR) basis functions because matrix representations of functions of coordinates are diagonal in the DVR. By diagonalizing matrices representing coordinates it is straightforward to obtain the DVR that corresponds to any direct product basis. Because contracted basis functions are eigenfunctions of reduced dimension Hamiltonians that include coupling terms they are not direct product functions. The advantages of contracted basis functions and the advantages of the DVR therefore appear to be mutually exclusive. A DVR that corresponds to contracted functions is unknown. In this paper we propose such a DVR. It spans the same space as a contracted basis, but in it matrix representations of coordinates are diagonal. The DVR basis functions are chosen to achieve maximal diagonality of coordinate matrices. We assess the accuracy of this DVR by applying it to model four-dimensional problems.     

Structural DNA profiles: single sequence queries

Structural DNA profiles use the structural properties of the constituent octamers either to observe any characteristics of a single sequence that are unusual (a single sequence query) or to visualize a pattern common to a set of sequences (a multiple sequence query). They are an aid in understanding structural reasons for functional DNA activity. Profiles that answer single sequence queries are introduced and Profile Manager (a software application developed to automate profile generation) is presented. Two sequences that are similar by their nucleotide composition but are known to be very different by structure are analyzed, resulting in useful illustrations that agree with the experimental nuclear magnetic resonance structures.     

New technologies in affinity assays to explore biological communication

The language that cells use to communicate consists of the small molecules, peptides, and proteins that are released into the extracellular environment. To decipher this language, analytical assays are needed that have high selectivity, high sensitivity, and fast temporal resolution. Affinity assays are a group of analytical methodologies that are adept at studying this communication. In this overview, we highlight several examples from the literature on various types of affinity assays used in different platforms to monitor biological communication of peptides and proteins.     

How to handle nanomaterials? The re-entry of individuals into the philosophy of chemistry

In this paper we will argue that the categories of physical individuals and chemical stuff are not sufficient to face the chemical ontology if nanomaterials are taken into account. From a perspective that considers ontological questions and wonders which the items involved in science are, we will argue that the domain of nanoscience must be considered as populated by entities that are neither individuals, as those of physics, nor stuff, as those items of macro-chemistry. This discussion, in virtue of the analysis of the nature of nanomaterials, leads to propose a proper ontological category for nanoparticles: nanoindividuals. Nanomaterials are sorts of individuals, but they are different from physical individuals and from chemical stuff. We will also claim to contribute to the growing field of the philosophy of chemistry, especially regarding discussions that manifest not only epistemological but also ontological issues. In this scenario, the field on nanoscience is particularly challenging.     

Features of the ESI mechanism that affect the observation of multiply charged noncovalent protein complexes and the determination of the association constant by the titration method

Several factors, attributable to the ESIMS mechanism, that can affect the assumptions of the titration method are examined: (1) The assumption that the concentrations in solution of the protein P, the ligand L, and the complex PL are proportional to the respective ion intensities observed with ESIMS, is examined with experiments in which ion intensities of two non-interacting proteins are compared with the respective concentrations. The intensities are found to be approximately proportional to the concentrations. The proportionality factors are found to increase as the mass of the protein is decreased. Very small proteins have much higher intensities. The results suggest that it is preferable to use only the intensity ratio of PL and P, whose masses are very close to each other when L is small, to determine the association constant KA in solution. (2) From the charge residue model (CRM) one expects that the solution will experience a very large increase of concentration due to evaporation of the precursor droplets, before the proteins P and PL are produced in the gas phase. This can shift the equilibrium in the droplets: P + L = PL, towards PL. Analysis of the droplet evaporation history shows that such a shift is not likely, because the time of droplet evolution is very short, only several micros, and the equilibrium relaxation time is much longer. (3) The droplet history shows that unreacted P and L can be often present together in the same droplet. On complete evaporation of such droplets L will land on P leading to PL and this effect will lead to values of KA that are too high. However, it is argued that mostly accidental, weakly bonded, complexes will form and these will dissociate in the clean up stages (heated transfer capillary and CAD region). Thus only very small errors are expected due to this cause. (4) Some PL complexes may have bonding that is too weak in the gas phase even though they have KA values in solution that predict high solution PL yields. In this case the PL complexes may decompose in the clean up stages and not be observed with sufficient intensity in the mass spectrum. This will lead to KA values that are too low. The effect is expected for complexes that involve significant hydrophobic interaction that leads to high stability of the complex in solution but low stability in the gas phase. The titration method is not suited for such systems.     

Brightening,Blinking, Bluing and Bleaching in the Life of a Quantum Dot: Friend or Foe?

Semiconductor nanocrystals or quantum dots (QDs) are highly photoluminescent materials with unique optical attributes that are being exploited in an ever‐increasing array of applications. However, the complex surface chemistry of these finite‐sized fluorophores gives rise to a number of photophysical phenomena that can complicate their use in imaging applications. Fluorescence intermittency (FI), photoluminescence enhancement (PLE) and spectral bluing are properties of QD emission that would appear, at first sight, detrimental to quantitative measurement. Fortunately, developments in rational QD synthesis and surface modification are promising to minimize the effects of these fluorescence instabilities, while applications that exploit them are now coming to the fore. We review recent experimental and theoretical studies of FI, PLE and bluing, highlighting the benefits, as well as complications, they bring to key applications.     

Conformational Selection of Dimethylarginine Recognition by the Survival Motor Neuron Tudor Domain

Tudor domains bind to dimethylarginine (DMA) residues, which are post‐translational modifications that play a central role in gene regulation in eukaryotic cells. NMR spectroscopy and quantum calculations are combined to demonstrate that DMA recognition by Tudor domains involves conformational selection. The binding mechanism is confirmed by a mutation in the aromatic cage that perturbs the native recognition mode of the ligand. General mechanistic principles are delineated from the combined results, indicating that Tudor domains utilize cation–π interactions to achieve ligand recognition.     

Reachability,persistence, and constructive chemical reaction networks (part III): a mathematical formalism for binary enzymatic networks and application to persistence

Chemical Reaction Network Theory is concerned with understanding the properties of systems of reactions from their structure. Enzymatic networks receive significant attention in the field because they are crucial in biochemistry and often illustrate the network features that are studied. In this paper we propose a formalism for binary enzymatic networks which can be used to research their mathematical properties. The networks are binary in that every enzyme-substrate complex consists of one enzyme and one substrate. Many connected concepts, e.g. futile enzymatic cycles and enzymatic cascades, are defined rigorously and so as to reflect the corresponding biochemical phenomena. We prove that binary enzymatic networks that are futile and cascaded are vacuously persistent: no species will tend to extinction if all species are implicitly present at initial time. This result extends prior work of Angeli, De Leenheer and Sontag in which a theorem was applied to show that certain particular enzymatic networks are persistent. This paper completes a series of three articles. It applies both the first paper which studies vacuous persistence and the second paper which describes a formalism for species composition.     

人尿中氟含量的测定及其意义

采用氟离子选择电子法对右江民族医学院28名≥19岁的成年健康学生(其中男生18名,女生10名)早上和晚上尿样分别进行了氟含量测定。结果表明,早上和晚上尿样尿氟含量有一定差异,而早上尿样中的氟含量小于晚上尿样。可认为从早到晚的时段内,人体从食物、水源或其它途径摄入了氟,从而出现了差异;样品氟含量的最大值0.959 mg/L在百色地区正常人尿氟百分位数法(P25～P97.5)正常值范围0.589～2.268 mg/L内,可认为右江民族医学院的人员未出现氟中毒,处于一个氟安全的地区。