Surface‐based protein binding pocket similarity

Protein similarity comparisons may be made on a local or global basis and may consider sequence information or differing levels of structural information. We present a local three‐dimensional method that compares protein binding site surfaces in full atomic detail. The approach is based on the morphological similarity method which has been widely applied for global comparison of small molecules. We apply the method to all‐by‐all comparisons two sets of human protein kinases, a very diverse set of ATP‐bound proteins from multiple species, and three heterogeneous benchmark protein binding site data sets. Cases of disagreement between sequence‐based similarity and binding site similarity yield informative examples. Where sequence similarity is very low, high pocket similarity can reliably identify important binding motifs. Where sequence similarity is very high, significant differences in pocket similarity are related to ligand binding specificity and similarity. Local protein binding pocket similarity provides qualitatively complementary information to other approaches, and it can yield quantitative information in support of functional annotation. Proteins 2011; © 2011 Wiley‐Liss, Inc.     

Post-Fire Resource Redistribution in Desert Grasslands: A Possible Negative Feedback on Land Degradation

Desert grasslands, which are very sensitive to external drivers like climate change, are areas affected by rapid land degradation processes. In many regions of the world the common form of land degradation involves the rapid encroachment of woody plants into desert grasslands. This process, thought to be irreversible and sustained by biophysical feedbacks of global desertification, results in the heterogeneous distribution of vegetation and soil resources. Most of these shrub-grass transition systems at the desert margins are prone to disturbances such as fires, which affect the interactions between ecological, hydrological, and land surface processes. Here we investigate the effect of prescribed fires on the landscape heterogeneity associated with shrub encroachment. Replicated field manipulation experiments were conducted at a shrub-grass transition zone in the northern Chihuahuan desert (New Mexico, USA) using a combination of erosion monitoring techniques, microtopography measurements, infiltration experiments, and isotopic studies. The results indicate that soil erosion is more intense in burned shrub patches compared to burned grass patches and bare interspaces. This enhancement of erosion processes, mainly aeolian, is attributed to the soil–water repellency induced by the burning shrubs, which alters the physical and chemical properties of the soil surface. Further, we show that by enhancing soil erodibility fires allow erosion processes to redistribute resources accumulated by the shrub clumps, thereby leading to a more homogeneous distribution of soil resources. Thus fires counteract or diminish the heterogeneity-forming dynamics of land degradation associated with shrub encroachment by enhancing local-scale soil erodibility. Author Contributions  SR—Conceived of or designed study, performed research, analyzed data, wrote the paper; PD—Conceived of or designed study, performed research, wrote the paper; LW—Performed research, analyzed data; GO—Contributed new methods, analyzed data; SC—Conceived of or designed study; CW—Performed research, contributed new methods or models; and SM—Contributed new methods or models.     

MHD plasma stabilization in a chain of axisymmetric adiabatic open mirror cells

Conditions for convective plasma instability in a chain of axisymmetric adiabatic mirror cells with different signs of magnetic field curvature are analyzed. The boundaries of the region that can be occupied by a stable hollow plasma in a system of two connected cells—a nonparaxial simple mirror cell and a semicusp—are determined, as well as the interval of allowed values of the ratio between the pressures in the cells. Because of the large magnetic field curvature in the component cells, the safety factor that is achieved at both—external and internal—plasma boundaries in accordance with the average min-B principle can be high. It is assumed that the unperturbed pressure in each cell is almost isotropic, in which case the mirror ratio should necessarily be large. A key role in the stability of the plasma is played by its compressibility. A comparison is made between the conditions for complete plasma stabilization against arbitrary perturbations and the conditions for stability of individual cells against the global mode. The stability of the cells against the global mode is sufficient, but not necessary, for stabilizing the chain. The analysis is done by using orthogonal coordinates associated with the unperturbed magnetic field (flux variables). Numerical simulations were carried out for nonparaxial cells from a certain three-parameter family.     

Responses of blowfly motion-sensitive neurons to reconstructed optic flow along outdoor flight paths

The retinal image flow a blowfly experiences in its daily life on the wing is determined by both the structure of the environment and the animal’s own movements. To understand the design of visual processing mechanisms, there is thus a need to analyse the performance of neurons under natural operating conditions. To this end, we recorded flight paths of flies outdoors and reconstructed what they had seen, by moving a panoramic camera along exactly the same paths. The reconstructed image sequences were later replayed on a fast, panoramic flight simulator to identified, motion sensitive neurons of the so-called horizontal system (HS) in the lobula plate of the blowfly, which are assumed to extract self-motion parameters from optic flow. We show that under real life conditions HS-cells not only encode information about self-rotation, but are also sensitive to translational optic flow and, thus, indirectly signal information about the depth structure of the environment. These properties do not require an elaboration of the known model of these neurons, because the natural optic flow sequences generate—at least qualitatively—the same depth-related response properties when used as input to a computational HS-cell model and to real neurons.     

A determination of the minimum sizes of representative volume elements for the prediction of cortical bone elastic properties

At its highest level of microstructural organization—the mesoscale or millimeter scale—cortical bone exhibits a heterogeneous distribution of pores (Haversian canals, resorption cavities). Multi-scale mechanical models rely on the definition of a representative volume element (RVE). Analytical homogenization techniques are usually based on an idealized RVE microstructure, while finite element homogenization using high-resolution images is based on a realistic RVE of finite size. The objective of this paper was to quantify the size and content of possible cortical bone mesoscale RVEs. RVE size was defined as the minimum size: (1) for which the apparent (homogenized) stiffness tensor becomes independent of the applied boundary conditions or (2) for which the variance of elastic properties for a set of microstructure realizations is sufficiently small. The field of elastic coefficients and microstructure in RVEs was derived from one acoustic microscopy image of a human femur cortical bone sample with an overall porosity of 8.5%. The homogenized properties of RVEs were computed with a finite element technique. It was found that the size of the RVE representative of the overall tissue is about 1.5 mm. Smaller RVEs (~0.5 mm) can also be considered to estimate local mesoscopic properties that strongly depend on the local pores volume fraction. This result provides a sound basis for the application of homogenization techniques to model the heterogeneity of cortical microstructures. An application of the findings to estimate elastic properties in the case of a porosity gradient is briefly presented.     

Maximizing biodiversity, information and sustainability

Numerous global changes—notably anthropogenic extinction—force reconsideration of our management practices and the ways we regulate human influence in today’s world. Here, I define management to maximize biodiversity and illustrate the science that provides information to set goals for such management. Maximizing biodiversity simultaneously achieves sustainability and systemic health by avoiding the abnormal or pathological. The normal or sustainable are determined through the use of empirical integrative patterns to objectively account for the complexity of systems within which we find ourselves as a species. The science that reveals these integrative patterns provides measures of problems that can be solved by maximizing biodiversity—problems heretofore recognized only qualitatively. I use the Shannon-Weiner information index to test, and, with no surprise, reject the null hypothesis that there is no direct anthropogenic effect on biodiversity. The results of this science serve as examples of the kind of information most useful for guiding management and illustrate maximized biodiversity as a standard for management. Reference points based on maximized biodiversity are preferable to statistical parameters in meeting the objective of avoiding the abnormal or pathological in our interactions with other species, ecosystems and the biosphere. Management to maximize biodiversity is implemented by modifying human interactions with other biotic systems to achieve consistency in such interactions by mimicking natural role models of sustainability. Human influence is a significant factor in today’s world and the magnitude of such influence is illustrated by comparing humans with other species.     

Critical conditions for phytoplankton blooms

We motivate and analyse a reaction—advection—diffusion model for the dynamics of a phytoplankton species. The reproductive rate of the phytoplankton is determined by the local light intensity. The light intensity decreases with depth due to absorption by water and phytoplankton. Phytoplankton is transported by turbulent diffusion in a water column of given depth. Furthermore, it might be sinking or buoyant depending on its specific density. Dimensional analysis allows the reduction of the full problem to a problem with four dimensionless parameters that is fully explored. We prove that the critical parameter regime for which a stationary phytoplankton bloom ceases to exist, can be analysed by a reduced linearized equation with particular boundary conditions. This problem is mapped exactly to a Bessel function problem, which is evaluated both numerically and by asymptotic expansions. A final transformation from dimensionless parameters back to laboratory parameters results in a complete set of predictions for the conditions that allow phytoplankton bloom development. Our results show that the conditions for phytoplankton bloom development can be captured by a critical depth, a compensation depth, and zero, one or two critical values of the vertical turbulent diffusion coefficient. These experimentally testable predictions take the form of similarity laws: every plankton—water—light-system characterized by the same dimensionless parameters will show the same dynamics.     

From the salt marsh to the ID-card: Bacteriorhodopsin as a functional material in nanobiotechnology

Bacteriorhodopsin (BR) is an evolutionary highly optimized photochromic retinal protein, which is found in extremely halophilic bacteria, e.g., in salt marshes. We demonstrated that starting from the wildtype as a blueprint by means of gene technology and biotechnology a versatile material for optical information recording can be developed. BR is structurally related to the visual pigment rhodopsin. It is the key molecule in the halobacterial photosynthetic system — an alternative to the chlorophyll-dependent photosynthesis. Its biological function ist that of a light-driven proton pump. In the halobacterial cell — which are found e.g. in salt marshes — it converts light energy into chemical energy, i.e. a proton gradient over the cell membrane, which finally supplies ATP to the cell. The photochromic properties of BR are very attractive compared to those of known organic photochromic compounds, in particular as far as longevity under exposure to oxygen and light is concerned. This is one of the reasons why we try to utilized this evolutionary optimized biomaterial for technical applications in particular in optical data storage and processing. As the biological function of BR is optimized for energy conversion, the physical properties of BR need to be tuned to turn this molecule into a material which matches the requirements of optical applications in data storage and processing. Gene technology is a powerful tool for the controlled modification of physical properties of a biomolecule like BR. In technical applications water needs to be omitted. However, the function of biomaterials strictly depends on the presence of water. Membrane proteins are much less dependent on the presence of water which makes them good candidates for technical applications. We showed that BR can be processed into dry polymeric films where its function is preserved. In a field test where ID-cards comprising BR-based inks as security elements it has been demonstrated that biomaterials may be integrated in active form as functional components into conventional technical applications. Conventional nanomaterials supply properties to a product, biomaterials supply functions.     

Sequential assignment of the proton NMR spectrum of isolated alpha(CO) chains from human adult hemoglobin.

In this paper we report proton two-dimensional NMR experiments on isolated alpha chains from human hemoglobin A (HbA) in the monocarboxylated state. Several J-correlated and NOE spectra in water or deuterium water and phosphate buffer (100 mM) at 310 K and pH 5.6 were acquired and analysed for the sequential assignment of the proton resonances. In addition, we used the topological data obtained from the crystal structure of alpha subunits in the monocarboxylated HbA tetramer. The assigned resonances correspond to 70% of the amino acid residues. The present results provide information on the tertiary structure of isolated alpha chains in solution, particularly in the heme region. This structure may be compared with that of the a subunits in the tetrameric HbA(CO) in crystal by comparison of observed chemical shifts and those calculated from the X-ray atomic coordinates. Overall, the global folding of the two forms are highly similar. However, this analysis points out several local conformational differences in the heme pocket and the neighboring of the unique Trp residue. Possible explanations of these differences are discussed.     

A Connected-cluster of hydration around myoglobin: Correlation between molecular dynamics simulations and experiment

An analysis of a molecular dynamics simulation of metmyoglobin in an explicit solvent environment of 3,128 water molecules has been performed. Both statics and dynamics of the protein-solvent interface are addressed in a comparison with experiment. Three-dimensional density distributions, temperature factors, and occupancy weights are computed for the solvent by using the trajectory coordinates. Analysis of the hydration leads to the localization of more than 500 hydration sites distributed into multiple layers of solvation located between 2.6 and 6.8 Å from the atomic protein surface. After locating the local solvent density maxima or hydration sites we conclude that water molecules of hydration positions and hydration sites are distinct concepts. Both global and detailed properties of the hydration cluster around myoglobin are compared with recent neutron and X-ray data on myoglobin. Questions arising from differences between X-ray and neutron data concerning the locations of the protein-bound water are investigated. Analysis of water site differences found from X-ray and neutron experiments compared with our simulation shows that the simulation gives a way to unify the hydration picture given by the two experiments. © 1994 John Wiley & Sons, Inc.     

Mathematical models of predator/prey/plant interactions in a patch environment

Several tritrophic systems are characterized by local over-exploitation of the food source. Interactions between predatory mites, spider mites and their host plants are an example of such systems: either the spider mites over-exploit local patches of host plants or the spider mites are exterminated by predatory mites. It is often stated that modelling the overall population dynamics of such systems in a realistic way would soon lead to an unmanageable edifice. We advocate, however, the use of physiologically structured population models as a both general and formal mathematical framework. The advantage is that analytically tractable models may be obtained from the complex ‘master’ model by time-scale arguments or special choices of model ingredients. In this way a network of models can be derived, each concentrating on a particular aspect, all inadequate to cover the entire spectrum, but together (we hope) providing a coherent set of insights the relative importance of which can be assessed by computer experiments on the ‘master’ model. In this paper a rather realistic model of predator/prey interactions in an ensemble of host-plant patches is presented and, as an example of our approach, some special cases are derived from that model. Their analysis provided some first, useful insights. It is shown that prolonged duration of the prey-dispersal phase and prey dispersal from predator (-invaded prey) patches may result in a stable steady state, whereas a humped plant-production function may — under certain conditions — result in two stable steady states.     

Conditions for Global Dynamic Stability of a Class of Resource-Bounded Model Ecosystems

This paper studies a class of dynamical systems that model multi-species ecosystems. These systems are ‘resource bounded’ in the sense that species compete to utilize an underlying limiting resource or substrate. This boundedness means that the relevant state space can be reduced to a simplex, with coordinates representing the proportions of substrate utilized by the various species. If the vector field is inward pointing on the boundary of the simplex, the state space is forward invariant under the system flow, a requirement that can be interpreted as the presence of non-zero exogenous recruitment. We consider conditions under which these model systems have a unique interior equilibrium that is globally asymptotically stable. The systems we consider generalize classical multi-species Lotka–Volterra systems, the behaviour of which is characterized by properties of the community (or interaction) matrix. However, the more general systems considered here are not characterized by a single matrix, but rather a family of matrices. We develop a set of ‘explicit conditions’ on the basis of a notion of ‘uniform diagonal dominance’ for such a family of matrices, that allows us to extract a set of sufficient conditions for global asymptotic stability based on properties of a single, derived matrix. Examples of these explicit conditions are discussed.     

Depth,contrast and view-based homing in outdoor scenes

Panoramic image differences can be used for view-based homing under natural outdoor conditions, because they increase smoothly with distance from a reference location (Zeil et al., J Opt Soc Am A 20(3):450–469, 2003). The particular shape, slope and depth of such image difference functions (IDFs) recorded at any one place, however, depend on a number of factors that so far have only been qualitatively identified. Here we show how the shape of difference functions depends on the depth structure and the contrast of natural scenes, by quantifying the depth- distribution of different outdoor scenes and by comparing it to the difference functions calculated with differently processed panoramic images, which were recorded at the same locations. We find (1) that IDFs and catchment areas become systematically wider as the average distance of objects increases, (2) that simple image processing operations—like subtracting the local mean, difference-of-Gaussian filtering and local contrast normalization—make difference functions robust against changes in illumination and the spurious effects of shadows, and (3) by comparing depth-dependent translational and depth-independent rotational difference functions, we show that IDFs of contrast-normalized snapshots are predominantly determined by the depth-structure and possibly also by occluding contours in a scene. We propose a model for the shape of IDFs as a tool for quantitative comparisons between the shapes of these functions in different scenes.     

Selenium in platelets

Blood and its main components are commonly used to detect states of selenium deficiency. In order to examine whether human platelets are able to provide better or additional information, improvements analytical method resulted in surprisingly narrow normal ranges for selenium and other mineral elements using neutron activation analysis (NAA) and atomic absorption spectrophotometry (AAS), and controlling thermal neutron flux, (n,γ)-cross sections, mean platelet wet wt, and water fraction of the platelets. Previously reported selenium concentrations in platelets on wet wt basis in the order of 500 ng/g—half of which had been found to derive from early bone marrow precursors using⁷⁴Se-selenite—were reproduced by NAA and AAS. However, with the new analytical method the selenium concentrations showed a narrower normal range than that of plasma. Moreover, platelet selenium did not in all cases correlate with plasma selenium. Cellular tissues such as platelets should, therefore, help to detect latent states of selenium deficiency.     

The theoretical investigation of one of the derivatives of 1, 2-dithienylcyclopentene as a molecular switch

The structural and electronic properties of a three-state molecular switch—an active device in a nano-electronic circuit—were studied using the B3LYP/6-31G* method. Due to its chemical stability, high conductivity upon doping, and non-linear optical properties, polythiophene is among the most widely studied conjugated organic polymers, both experimentally and theoretically. The aim of the present work was to theoretically study a very complex case: a three-state switch synthesized and experimentally investigated by Nishida et al. (Org Lett 6:2523–2526, 2004). An initial set of test calculations showed B3LYP level of theory and 6-31G* basis set to be the most appropriate for our purpose, i.e., the study of the structure, charge and spin distributions, as well as electrical characteristics such as electric polarizability, HOMO-LUMO gap (HLG) and electric dipole moment, for one of the 1,2-dithienylcyclopentene derivatives. Also, natural bond orbital analyses were performed to calculate local charges and charge transfers in order to study the capability of the molecule as a molecular switch. The results reported here are of general significance, and demonstrate that it is possible to use certain structural and electrical properties to understand and design electro-photochromic compounds showing a switching function in cases where stable forms can be exchanged by light or electron transfer. Figure Model of a thiophene wire incorporating a redox active unit     

Autocommunication and Perceptual Markers in Landscape: Japanese Examples

Juri Lotman distinguishes between two main types of communication. In addition to the classical I-YOU communication, he speaks about I-I communication, where both the addresser and the addressee are one and the same person. Contrary to how it sounds, autocommunication is not self-sufficient musing inside one’s self, it is remodelling oneself through a code from an entity outside oneself, be it animate or inanimate. According to Lotman, it is often the rhythmical phenomena like poetry, the rhythm of waves, etc. that lend themselves for the act of autocommunication as external codes. After having received the message one is not identical to the original oneself anymore. Perceptual markers of landscape—specific rhythms, ephemera, the rhythm of human everyday activities, bodily movement—can be considered as a secondary code leading to autocommunication in the person who contemplates the landscape. Looking at the landscape—which also implies the rhythmical movement of the eyes—one uses it as a code to reconstitute oneself. A person who has confronted a landscape does not leave it as the same person. The present article poses a definition of autocommunication in landscapes and discusses the way in which other sensorial information apart from the visual—smell, movement, rhythms etc—are used culturally to reinforce autocommunication with oneself. It can be said that several institutionalised religious and cultural practices expect the subject to reconstitute him- or herself mainly through the bodily landscape experience.     

Multi-scale calculation and global-fit analysis of hydrodynamic properties of biological macromolecules: determination of the overall conformation of antibody IgG molecules

We present a scheme, based on existing and newly developed computational tools, for the determination of the overall conformation of biological macromolecules composed by domains or subunits, using from such structural determination easily available solution properties. In a multi-scale approach, atomic-level structures are used to provide simple shapes for the subunits, which are put together in a coarse grained model, with a few parameters that determine the overall shape of the macromolecule. Computer programs, like those in the HYDRO suite that evaluate the properties of either atomic or coarse-grained models. In this paper we present a new scheme for a global fit of multiple properties, implemented in a new computer program, HYDROFIT, which interfaces with the programs of the HYDRO suite to find an optimum, best-fitting structure in a robust but simple way. The determination of the overall structure of the native antibody IgG3, bearing a long hinge, and that of the hingeless mutant m15 is presented to test and confirm the validity of this simple, systematic and efficient scheme.     

Trajectory NG: portable, compressed, general molecular dynamics trajectories

We present general algorithms for the compression of molecular dynamics trajectories. The standard ways to store MD trajectories as text or as raw binary floating point numbers result in very large files when efficient simulation programs are used on supercomputers. Our algorithms are based on the observation that differences in atomic coordinates/velocities, in either time or space, are generally smaller than the absolute values of the coordinates/velocities. Also, it is often possible to store values at a lower precision. We apply several compression schemes to compress the resulting differences further. The most efficient algorithms developed here use a block sorting algorithm in combination with Huffman coding. Depending on the frequency of storage of frames in the trajectory, either space, time, or combinations of space and time differences are usually the most efficient. We compare the efficiency of our algorithms with each other and with other algorithms present in the literature for various systems: liquid argon, water, a virus capsid solvated in 15 mM aqueous NaCl, and solid magnesium oxide. We perform tests to determine how much precision is necessary to obtain accurate structural and dynamic properties, as well as benchmark a parallelized implementation of the algorithms. We obtain compression ratios (compared to single precision floating point) of 1:3.3–1:35 depending on the frequency of storage of frames and the system studied.