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At least 361 records · Page 20Linked to original sources

PubMed2002

Amino acid sequence and structure modeling of savignin, a thrombin inhibitor from the tick, Ornithodoros savignyi.

The full-length gene of savignin, a potent thrombin (E.C. 3.4.21.5) inhibitor from the tick Ornithodoros savignyi has been cloned and sequenced. Both 5' and 3' UTR's, a signal peptide from the translated amino acid sequence and an unusual poly-adenylation signal (AATACA) has been identified. The translated protein sequence shows high identity (63%) with ornithodorin, the thrombin inhibitor from the tick, Ornithodoros moubata. Molecular modeling using the structure of ornithodorin as reference gave a structure with an RMSD of 0.25 A for the full-length protein, 0.11 A for the N-terminal BPTI-like domain and 0.11 A for the C-terminal BPTI-like domain, indicating that maximum deviation occurs in the mobile bridge (0.18 A) between the two domains. Docking of savignin to thrombin shows that the interaction is similar to the ornithodorin-thrombin complex. The N-terminal amino acid residues of savignin bind inside the active site cleft, while the C-terminal domain of savignin has a net negative electrostatic potential and interacts with the basic fibrinogen recognition exosite of thrombin through hydrogen bonds and hydrophobic interactions. These results correlate with kinetic data obtained, which showed that savignin is a competitive, slow, tight-binding inhibitor that requires thrombin's fibrinogen-binding exo-site for optimal inhibition.

Amino Acid Sequence↗

PubMed2001

Comparison study of different head model structures with homogeneous/inhomogeneous conductivity.

Most of the human head models used in dipole localisation research, which have been reported in the literature to date, assume a simplified cranial structure wherein the head is modelled as a set of distinct homogenous tissue compartments. The inherent inhomogeneity of the tissues has so far been ignored in these models due to the difficulties involved in obtaining the conductivity characteristics with sufficiently high enough spatial resolution throughout the head. A technique for developing an inhomogeneous head model based on the generation of pseudo-conductivity values from the existing but sparse conductivity values is proposed in this paper. Comparative studies are conducted on different model structures and different mechanisms for generating the pseudo conductivities. An evaluation of the results of these studies as reported in this paper, shows that contrary to current simplifying assumptions, tissue inhomogeneity has a major influence on the computation of electrical potential distributions in the head.

Brain↗

PubMed1996

Transition rate kinetics from ethanol oxidation to glucose utilisation within a structured model of baker's yeast.

The transition rate kinetics from ethanol oxidation to glucose utilisation, within a structured model of baker's yeast, described previously, were experimentally identified. The shift in metabolism has been assessed through glucose pulses during batch growth on ethanol. The influence of glucose concentration (between 0.25 g l-1 and 0.90 g l-1) and initial biomass concentration (between 0.61 g l-1 and 1.44 g l-1) on the transition rate was determined. The transition rate can not be described by a first-order saturation-type kinetics with respect to glucose only. A corrective term, which takes into account biomass concentration should be included.

Culture Media↗

PubMed2003

A track structure model for simulation of strand breaks in plasmid DNA after heavy ion irradiation.

We present a track structure model based on the local dose deposited around heavy ion tracks to explain the cross sections for single-strand and double-strand break induction in plasmid DNA in different aqueous buffers. The model is based only on measurable quantities, namely the effect distribution for inducing strand breaks after x-ray irradiation as a function of dose, and the radial dose distribution of the heavy ion track. The effect of indirect DNA damage mediated by free radicals produced in the water surrounding the DNA is accounted for by allowing the radial dose distribution to be smeared in space by an effective target size corresponding to the squared sum of the geometrical extension of the plasmid molecule and the mean free drift path of the radicals in the buffer solution. Our calculations reproduce well the measured cross sections for single-strand and double-strand break induction in SV40 plasmid DNA in various buffer solutions both as a function of the LET and of the specific energy of the heavy ion.

Buffers↗

PubMed1988

Structural model for an oligonucleotide containing a bulged guanosine by NMR and energy minimization.

We present three-dimensional structural models for a DNA oligomer containing a bulged guanosine based on proton NMR data and energy minimization computations. The nonexchangeable proton resonances of the duplex 5'd(GATGGGCAG).d(CTGCGCCATC) are assigned by nuclear Overhauser effect spectroscopy (NOESY) and correlated spectroscopy connectivities, and the NMR spectrum is compared with that of a regular 8-mer of similar sequence, 5'd(GATGGCAG).d(CTGCCATC). Experimental proton-proton distances are obtained from NOESY spectra acquired with mixing times of 100, 150, and 200 ms. A refined three-dimensional structure for the bulge-containing duplex is calculated from regular B DNA starting coordinates by using the AMBER molecular mechanics program [Weiner, S. J., Kollman, P. A., Case, D. A., Singh, U. C., Ghio, C., Alagona, G., Profeta, S., & Weiner, P. (1984) J. Am. Chem. Soc. 106, 765-784]. We compare structures obtained by building the helix in three and four base pair increments with structures obtained by direct minimization of the entire nine base sequence, with and without experimental distance constraints. The general features of all the calculated structures are very similar. The helix is of the B family, with the extra guanine stacked into the helix, and the helix axis is bent by 18-23 degrees, in agreement with gel mobility data for bulge-containing sequences [Rice, J. A. (1987) Ph.D. Thesis, Yale University].

Base Sequence↗

PubMed1995

A structural model of the dimensions of teacher stress.

A comprehensive survey of teacher stress, job satisfaction and career commitment among 710 full-time primary school teachers was undertaken by Borg, Riding & Falzon (1991) in the Mediterranean islands of Malta and Gozo. A principal components analysis of a 20-item sources of teacher stress inventory had suggested four distinct dimensions which were labelled: Pupil Misbehaviour, Time/Resource Difficulties, Professional Recognition Needs, and Poor Relationships, respectively. To check on the validity of the Borg et al. factor solution, the group of 710 teachers was randomly split into two separate samples. Exploratory factor analysis was carried out on the data from Sample 1 (N = 335), while Sample 2 (N = 375) provided the cross-validational data for a LISREL confirmatory factor analysis. Results supported the proposed dimensionality of the sources of teacher stress (measurement model), along with evidence of an additional teacher stress factor (Workload). Consequently, structural modelling of the 'causal relationships' between the various latent variables and self-reported stress was undertaken on the combined samples (N = 710). Although both non-recursive and recursive models incorporating Poor Colleague Relations as a mediating variable were tested for their goodness-of-fit, a simple regression model provided the most parsimonious fit to the empirical data, wherein Workload and Student Misbehaviour accounted for most of the variance in predicting teaching stress.

Adult↗

PubMed1978

Finite element dynamic structural model of the human thorax for chest impact response and injury studies.

The component model modal synthesis technique has been successfully adapted to the finite element structural dynamic model of the human thorax for chest impact response and injury studies. The complete thorax was modeled as an assembly of a thorax module with viscera subsystems. The module was further subdivided into rib components. Major model development was conducted at the component level to provide cost saving and modeling flexibility. The results show that the thorax can be successfully treated as a linear system. A two-step procedure was developed to obtain viscera response. The analysis results of THORAX III, a first cut thorax model, were favorably compared with Kroell-Nahum cadaver experiments. The sensitivity of the chest response due to variation in input pulse shape and peak force were analyzed. The pulse shape can affect the force-deflection relationships while peak force affects the peak response. Further sensitivity studies and experiments are proposed.

Biomechanical Phenomena↗

PubMed1998

A new structural model for P-glycoprotein.

Multidrug resistance to anti-cancer drugs is a major medical problem. Resistance is manifested largely by the product of the human MDR1 gene, P-glycoprotein, an ABC transporter that is an integral membrane protein of 1280 amino acids arranged into two homologous halves, each comprising 6 putative transmembrane alpha-helices and an ATP binding domain. Despite the plethora of data from site-directed, scanning and domain replacement mutagenesis, epitope mapping and photoaffinity labeling, a clear structural model for P-glycoprotein remains largely elusive. In this report, we propose a new model for P-glycoprotein that is supported by the vast body of previous data. The model comprises 2 membrane-embedded 16-strand beta-barrels, attached by short loops to two 6-helix bundles beneath each barrel. Each ATP binding domain contributes 2 beta-strands and 1 alpha-helix to the structure. This model, together with an analysis of the amino acid sequence alignment of P-glycoprotein isoforms, is used to delineate drug binding and translocation sites. We show that the locations of these sites are consistent with mutational, kinetic and labeling data.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Structural model of human IL-13 defines the spatial interactions with the IL-13Ralpha/IL-4Ralpha receptor.

Interleukin-13 (IL-13) plays a key role in immune responses and inflammation. A structural model of human IL-13 (HuIL-13) based on the nuclear magnetic resonance and X-ray structure of IL-4 is put forward. Unlike previous models, this model is based on new sequence alignments that take into account the formation of the two disulfide linkages that have been determined experimentally. The proposed structure of human IL-13 is similar to IL-4, consisting of a four helix bundle with hydrophobic residues lining the core of the molecule and surface polar residues showing a high degree of solvent accessibility. Regions of HuIL-13 that are critical for the interaction with its receptors are explored and discussed in relation to existing mutagenic studies. From these studies we predict that helices A and C of HuIL-13 interact with the IL-4 receptor alpha (IL-4Ralpha) region and helix D is responsible for the interaction with the IL-13 receptor alpha 1 (IL-13Ralpha1) receptor.

Amino Acid Sequence↗

PubMed1993

DNA-binding properties and secondary structural model of the hepatocyte nuclear factor 3/fork head domain.

An 84-amino acid segment of QRF-1 [glutamine (Q)-rich factor 1], a newly cloned, B-cell-derived DNA-binding protein, shows significant sequence homology with the DNA-binding domains of the hepatocyte nuclear factor 3/fork head family of proteins. Here we demonstrate that this 84-amino acid domain is necessary and sufficient for DNA binding. We also propose a secondary structural model for the domain. At the N-terminal portion of the model, a basic hook structure is followed by two amphipathic helices separated by a turn. Invariant amino acid residues within the two proposed helices form the hydrophobic cores. An aromatic kink and a third amphipathic helix comprise the center of the domain. At the C terminus, two variable-length loops flank a putative 7-amino acid helix followed by a short basic region.

Amino Acid Sequence↗

PubMed1998

Identification of conserved amino acids in murine B7-1IgV domain critical for CTLA4/CD28:B7 interaction by site-directed mutagenesis: a novel structural model of the binding site.

The B7: CD28/CTLA4 interaction plays a major role in T cell responses. Immune intervention targeted at this interaction has demonstrated a vast potential in enhancing tumor immunity and blocking autoimmunity and transplant rejection. However, the structural basis for this interaction is unclear. While we and others have performed site-directed mutagenesis to define amino acids involved in binding CD28 and CTLA4, these residues are localized in different regions, and it is unlikely for all of them to be directly involved. In addition, the effect of the mutations on the overall conformation of B7 has not been systematically evaluated. In this study, we have carried out site-directed mutagenesis to define the amino acids within B7-1 IgV-like domain which participate B7:CD28/CTLA4 interaction. Four anti-B7-1 mAbs that recognize three independent antigenic epitopes on B7-1 were used to monitor the effect of mutations on the overall conformation of B7-1. Of the five mutations in the IgV domain that we have produced, D113 > A appears to interfere with cell surface expression and/or overall conformation of B7-1. while four others do not significantly affect the overall conformation and cell surface expression of B7-1. Among them, G115 > A and Y91 > A eliminated B7-1 binding to both CD28Ig and CTLA4Ig; our previously reported mutants L109 > A and W88 > A selectively affect the B7-1 binding to either CD28Ig or CTLA4Ig. Structural modeling of B7-1 based on the structure of immunoglobulin revealed that these four and other previously identified critical amino acids in both IgV- and IgC-like domains can form a localized structure.

Abatacept↗

PubMed2006

Lagged covariance structure models for studying functional connectivity in the brain.

Most cognitive processes are supported by large networks of brain regions. To describe the operation of these networks, it is critical to understand how individual areas are functionally connected. Here, we establish a statistical framework for studying effective and functional brain connectivity, using data obtained with a relatively new neuroimaging method, the event-related optical signal (EROS). The novelty of our approach is the use of timing information (in the form of lagged cross-correlations) in interpreting the connections between areas. Interpretation of lagged cross-correlations exploits the combination of spatial and temporal resolution provided by EROS. In this paper, we apply dynamic factor analysis as a method for testing various structural models on the lagged covariance matrices derived from the EROS data. We first illustrate the approach by testing a simple path model of neural activity propagation from area V1 to V3 in a visual stimulation task. We then build more complex structural equation models with latent variables, describing both within-hemisphere integrity, and interactions between the two hemispheres, to interpret data from a second task involving inter-hemispheric competition. The results demonstrate how the integrity of anatomical connections between the two hemispheres explains different patterns of cross-hemispheric interactions. This approach allows for fitting brain imaging data to complex models that capture dynamic cognitive processes as they rapidly evolve over time.

Adolescent↗

PubMed2004

Structured model of influenza virus replication in MDCK cells.

Intracellular events that take place during influenza virus replication in animal cells are well understood qualitatively. However, to better understand the complex interaction of the virus with its host cell and to quantitatively analyze the use of cellular resources for virion formation or the overall dynamic for the entire infection cycle, a mathematical model for influenza virus replication has to be formulated. Here, we present a structured model for the single-cell reproductive cycle of influenza A virus in animal cells that accounts for the individual steps of the process such as attachment, internalization, genome replication and translation, and progeny virion assembly. The model describes an average cell surrounded by a small quantity of medium and infected by a low number of virus particles. The model allows estimation of the cellular resources consumed by virus replication. Simulation results show that the number of cellular surface receptors and endosomes, as well as other resources, such as the number of free nucleotides or amino acids, is not significantly influenced by influenza virus propagation. A factor that limits the growth rate of progeny viruses and their release is the total amount of matrix proteins (M1) in the nucleus while other newly synthesized viral proteins (e.g., nucleoprotein NP) and viral RNAs accumulate. During budding, synthesis of vRNPs (viral ribonucleoprotein complexes) represents another limiting factor. Based on this model it is also possible to analyze effects of parameter changes on the dynamics of virus replication, to identify possible targets for molecular engineering, or to develop strategies for improving yields in vaccine production processes. Furthermore, a better insight into the interactions of viruses and host cells might help to improve our understanding of virus-related diseases and to develop therapies.

Animals↗

PubMedDate not supplied

A theory of planned behavior-based structural model for breast-feeding.

BACKGROUND: Breast-feeding is the recommended method of infant feeding because it is clearly associated with health benefits for infants and their mothers. Yet, many women who initiate breast-feeding fail to meet their own personal goals or recommended standards for duration of breast-feeding. OBJECTIVE: To refine a Theory of Planned Behavior (TPB)-based structural model for explaining variability in breast-feeding intention and duration. METHOD: The study design was prospective, multicorrelational, and longitudinal. Out of the total sample of 635 women, 602 mothers of healthy, full-term infants provided complete datasets over the entire course of their breast-feeding experience and these datasets were used in the modeling analyses. Simultaneous multisample analysis of covariance structures was used to develop the model. RESULTS: The resulting TPB for Breast-Feeding (TPB-BrF) describes the rational, motivational processes of the original TPB, but reconfigures the relationships among them, for homemakers (TPB-BrF/H), women employed half-time or less (TPB-BrF/EL), and women employed more than half-time (TPB-BrF/EM). Mothers' early postpartum ratings of adequacy of milk supply and stimulus conditions of maternal education and breast-feeding knowledge were included in the TPB-BrF to better explain breast-feeding outcomes. Model complexity increased with employment effort. CONCLUSION: The TPB-BrF is a comprehensive, theoretically based, empirically verified model that can serve as a useful heuristic for understanding the personal motivational components of breast-feeding behavior.

Adult↗

PubMed1998

Spatial structure model of the CD4 receptor-binding site of the HIV envelope protein gp120.

In this study we have undertaken attempt to predict 3D structure of the CD4 receptor-binding site of the HIV envelope protein gp120. The structure of this site has been constructed by the analysis of low-energy conformers of peptide T, an HIV reproduction inhibitor with amino acid sequence corresponding to the fragment Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr of protein gp120, ensuring the interaction of virus with T4 lymphocytes. To do this, the following researches have been carried out: i) the spatial structure models of peptide T and similar fragment 4-11 of an analogues of vasoactive intestinal peptide have been modeled by the restrained molecular mechanics method developed earlier, ii) conformational parameters of these models have been compared to geometrical characteristics of homologous segments of unrelated proteins with known spatial structures. The following major conclusions have been made based on the comparative analysis: i) the conformation of C-terminal fragment Thr-Thr-Asn-Tyr-Thr of peptide T, responsible for the biological activity of the molecule, does not undergo the essential distortions while embedding into the peptide chains of unrelated proteins; ii) this conformation, that is realized in isolated molecule and includes two consecutive reverse turns of the polypeptide chain, adequately describes the main conformational features of an appropriate site of the HIV protein gp120; iii) the fragment Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr of protein gp120 accepts one of six spatial forms which are characteristic for peptide T.

Binding Sites↗

PubMed1982

A structural model of human erythrocyte spectrin. Alignment of chemical and functional domains.

Proteolytic susceptibility has been used to probe the structure of human erythrocyte spectrin. Nine unique polypeptide segments have been defined by mild trypsin digestion (0 degrees C) and analyzed by two-dimensional peptide mapping techniques. These peptide segments, referred to operationally as chemical domains, exhibited varying degrees of sensitivity to further proteolytic cleavage. One region (beta I) which contained the phosphorylated amino acids of the beta subunit was quite sensitive to proteolysis and was rapidly degraded to numerous small peptides. Overlap peptides produced by enzymatic and chemical cleavages were used to align each domain in the appropriate spectrin subunit. The molecular weights of the largest unique peptides from both subunits sum to the approximate weight of the intact molecule. Similarly, summation of the two-dimensional peptide maps of the intermediate sized peptides approximates the two-dimensional maps of the intact spectrin subunits, indicating that most or all of the molecule is represented. These results suggest that spectrin is composed of multiple, ordered, largely alpha-helical domains that are connected by small protease-sensitive segments. A comprehensive structural model is presented.

Electrophoresis, Cellulose Acetate↗

PubMed1998

Global stability of an age-structure model for TB and its applications to optimal vaccination strategies.

This article focuses on the study of an age-structure model for the disease transmission dynamics of tuberculosis in populations that are subjected to a vaccination program. We first show that the infection-free steady state is globally stable if the basic reproductive number R0 is below one, and that an endemic steady state exists when the reproductive number in the presence of vaccine is above one. We then apply the theoretical results to vaccination policies to determine the optimal age or ages at which an individual should be vaccinated. It is shown that the optimal strategies can be either one- or two-age strategies.

Age Distribution↗

PubMed1991

Building structural models of peptides: a semi-automatic software.

We present a software package that allows the construction and display of structural models of proteins starting from the amino acid sequence written in the one-letter code of standard data bank format. The software includes a very fast and efficient algorithm aimed at finding the global energy minimum of the potential function describing the molecular interactions. The whole package is conceived to have maximum flexibility. Completely automatic procedures are envisaged for standard problems. For non-standard problems, the construction procedure can be interactively adopted to meet with different options.

Algorithms↗