Data Bank (data + bank)

Distribution by Scientific Domains

Kinds of Data Bank

  • protein data bank


  • Selected Abstracts


    Thermus thermophilus Glycosynthases for the Efficient Synthesis of Galactosyl and Glucosyl ,-(1,3) - Glycosides

    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2005
    Jullien Drone
    Abstract Inverting mutant glycosynthases were designed according to the Withers strategy, starting from wild-type Thermus thermophilus retaining Tt-,-Gly glycosidase. Directed mutagenesis of catalytic nucleophile glutamate 338 by alanine, serine, and glycine afforded the E338A, E338S, and E338G mutant enzymes, respectively. As was to be expected, the mutants were unable to catalyze the hydrolysis of the transglycosidation products. In agreement with previous results, the E338S and E338G catalysts were much more efficient than E338A. Moreover, our results showed that these enzymes were inactive in the hydrolysis of the ,- D -glycopyranosyl fluorides used as donors, and so suitable experimental conditions, under which the rate of spontaneous hydrolysis of the donor was considerably lower than that of enzymatic transglycosidation, provided galactosyl and glucosyl ,-(1,3) - glycosides in yields of up to 90,%. The structure of native Tt-,-Gly available in the Protein Data Bank offers a good basis for interpretation of our results by means of molecular modeling. Thus, in the case of the E338S mutant, a lower energy of the system was obtained when the donor and the acceptor were in the right position to form the ,-(1,3) - glycosidic bond. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source]


    Protein tandem repeats , the more perfect, the less structured

    FEBS JOURNAL, Issue 12 2010
    Julien Jorda
    We analysed the structural properties of protein regions containing arrays of perfect and nearly perfect tandem repeats. Naturally occurring proteins with perfect repeats are practically absent among the proteins with known 3D structures. The great majority of such regions in the Protein Data Bank are found in the proteins designed de novo. The abundance of natural structured proteins with tandem repeats is inversely correlated with the repeat perfection: the chance of finding natural structured proteins in the Protein Data Bank increases with a decrease in the level of repeat perfection. Prediction of intrinsic disorder within the tandem repeats in the SwissProt proteins supports the conclusion that the level of repeat perfection correlates with their tendency to be unstructured. This correlation is valid across the various species and subcellular localizations, although the level of disordered tandem repeats varies significantly between these datasets. On average, in prokaryotes, tandem repeats of cytoplasmic proteins were predicted to be the most structured, whereas in eukaryotes, the most structured portion of the repeats was found in the membrane proteins. Our study supports the hypothesis that, in general, the repeat perfection is a sign of recent evolutionary events rather than of exceptional structural and (or) functional importance of the repeat residues. [source]


    Copper-Binding Motifs: Structural and Theoretical Aspects

    HELVETICA CHIMICA ACTA, Issue 5 2003
    Amy Kaufman, Katz
    In this paper, we report the results of a study involving the coordination geometries of CuI, CuII, and CuIII crystal structures in the Cambridge Structural Database, and on Cu binding sites in proteins taken from the Protein Data Bank. The motifs used to bind two bridged Cu ions are also described. In addition, we report the results of ab initio molecular-orbital calculations performed on a variety of model CuI/CuII complexes (CuI/CuII,XnYm (X, Y=NH3, SH2); n+m=4; n=0,4) to provide data on the structural and energetic changes that occur in isolated complexes when the oxidation state of the Cu ion is changed from II to I while the coordination number is conserved. The use of such simple ligands in these calculations eliminates constraints on the geometric changes that may be imposed by more-complicated ligands. [source]


    The SAAPdb web resource: A large-scale structural analysis of mutant proteins,

    HUMAN MUTATION, Issue 4 2009
    Jacob M. Hurst
    Abstract The Single Amino Acid Polymorphism database (SAAPdb) is a new resource for the analysis and visualization of the structural effects of mutations. Our analytical approach is to map single nucleotide polymorphisms (SNPs) and pathogenic deviations (PDs) to protein structural data held within the Protein Data Bank. By mapping mutations onto protein structures, we can hypothesize whether the mutant residues will have any local structural effect that may "explain" a deleterious phenotype. Our prior work used a similar approach to analyze mutations within a single protein. An analysis of the contents of SAAPdb indicates that there are clear differences in the sequence and structural characteristics of SNPs and PDs, and that PDs are more often explained by our structural analysis. This mapping and analysis is a useful resource for the mutation community and is publicly available at http://www.bioinf.org.uk/saap/db/. Hum Mutat 0, 1,9, 2009. © 2009 Wiley-Liss, Inc. [source]


    Exploring the binding site of the human muscarinic M3 receptor: Homology modeling and docking study

    INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 8 2007
    Liliana Ostopovici
    Abstract The human muscarinic M3 receptor (hM3) and its interactions with selective agonists and antagonists were investigated by means of combined homology and docking approach. Also, two pharmacophoric models for the hM3 agonist and antagonist binding sites were proposed. The three-dimensional (3D) structure of hM3 receptor was modeled based on the high-resolution X-ray structure of bovine rhodopsin from the Protein Data Bank (PDB). To validate the reliability of the model obtained, the main chain torsion angles phi (,) and psi (,) were examined in a Ramachandran plot, and all omega angles were measured for peptidic bond planarity. The characteristics of the active site, the position, and the orientation of ligands in situ, as well as the binding modes of the representative agonists and antagonists, were analyzed by applying a molecular docking technique using the AutoDock 3.0.5 program. Specific interactions responsible for recognition of the hM3 receptor, like ionic bond formed between protonated amine of the ligands and the Asp3.6 side chain were identified. Structure,reactivity relationships have been explained by analyzing the 3D structure of the hM3 model and the ligand conformations resulted from molecular docking simulation. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source]


    PDB_REDO: automated re-refinement of X-ray structure models in the PDB

    JOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 3 2009
    Robbie P. Joosten
    Structural biology, homology modelling and rational drug design require accurate three-dimensional macromolecular coordinates. However, the coordinates in the Protein Data Bank (PDB) have not all been obtained using the latest experimental and computational methods. In this study a method is presented for automated re-refinement of existing structure models in the PDB. A large-scale benchmark with 16,807 PDB entries showed that they can be improved in terms of fit to the deposited experimental X-ray data as well as in terms of geometric quality. The re-refinement protocol uses TLS models to describe concerted atom movement. The resulting structure models are made available through the PDB_REDO databank (http://www.cmbi.ru.nl/pdb_redo/). Grid computing techniques were used to overcome the computational requirements of this endeavour. [source]


    Automatic inference of protein quaternary structure from crystals

    JOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 5 2003
    Hannes Ponstingl
    The arrangement of the subunits in an oligomeric protein often cannot be inferred without ambiguity from crystallographic studies. The annotation of the functional assembly of protein structures in the Protein Data Bank (PDB) is incomplete and frequently inconsistent. Instructions for the reconstruction, by symmetry, of the functional assembly from the deposited coordinates are often absent. An automatic procedure is proposed for the inference of assembly structures that are likely to be physiologically relevant. The method scores crystal contacts by their contact size and chemical complementarity. The subunit assembly is then inferred from these scored contacts by a clustering procedure involving a single adjustable parameter. When predicting the oligomeric state for a non-redundant set of 55 monomeric and 163 oligomeric proteins from dimers up to hexamers, a classification error rate of 16% was observed. [source]


    A generalized higher order kernel energy approximation method

    JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2010
    Stewart N. Weiss
    Abstract We present a general mathematical model that can be used to improve almost all fragment-based methods for ab initio calculation of total molecular energy. Fragment-based methods of computing total molecular energy mathematically decompose a molecule into smaller fragments, quantum-mechanically compute the energies of single and multiple fragments, and then combine the computed fragment energies in some particular way to compute the total molecular energy. Because the kernel energy method (KEM) is a fragment-based method that has been used with much success on many biological molecules, our model is presented in the context of the KEM in particular. In this generalized model, the total energy is not based on sums of all possible double-, triple-, and quadruple-kernel interactions, but on the interactions of precisely those combinations of kernels that are connected in the mathematical graph that represents the fragmented molecule. This makes it possible to estimate total molecular energy with high accuracy and no superfluous computation and greatly extends the utility of the KEM and other fragment-based methods. We demonstrate the practicality and effectiveness of our model by presenting how it has been used on the yeast initiator tRNA molecule, ytRN (1YFG in the Protein Data Bank), with kernel computations using the Hartree-Fock equations with a limited basis of Gaussian STO-3G type. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]


    Incorporating structural characteristics for identification of protein methylation sites

    JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 9 2009
    Dray-Ming Shien
    Abstract Studies over the last few years have identified protein methylation on histones and other proteins that are involved in the regulation of gene transcription. Several works have developed approaches to identify computationally the potential methylation sites on lysine and arginine. Studies of protein tertiary structure have demonstrated that the sites of protein methylation are preferentially in regions that are easily accessible. However, previous studies have not taken into account the solvent-accessible surface area (ASA) that surrounds the methylation sites. This work presents a method named MASA that combines the support vector machine with the sequence and structural characteristics of proteins to identify methylation sites on lysine, arginine, glutamate, and asparagine. Since most experimental methylation sites are not associated with corresponding protein tertiary structures in the Protein Data Bank, the effective solvent-accessible prediction tools have been adopted to determine the potential ASA values of amino acids in proteins. Evaluation of predictive performance by cross-validation indicates that the ASA values around the methylation sites can improve the accuracy of prediction. Additionally, an independent test reveals that the prediction accuracies for methylated lysine and arginine are 80.8 and 85.0%, respectively. Finally, the proposed method is implemented as an effective system for identifying protein methylation sites. The developed web server is freely available at http://MASA.mbc.nctu.edu.tw/. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009 [source]


    Enveloping triangulation method for detecting internal cavities in proteins and algorithm for computing their surface areas and volumes

    JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 3 2009
    Ján Bu
    Abstract Detection and quantitative characterization of the internal cavities in proteins remain an important topic in studying protein structure and function. Here we propose a new analytical method for detecting the existence of cavities in proteins. The method is based on constructing the special enveloping triangulation enclosing the cavities. Based on this method, we develop an algorithm and a fortran package, CAVE, for computing volumes and surface areas of cavities in proteins. We first test our method and algorithm in some artificial systems of spheres and find that the calculated results are consistent with exact results. Then we apply the package to compute volumes and surface areas of cavities for some protein structures in the Protein Data Bank. We compare our calculated results with those obtained by some other methods and find that our approach is reliable. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 [source]


    Towards protein folding with evolutionary techniques

    JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 11 2005
    Florian Koskowski
    Abstract We present design details and first tests of a new evolutionary algorithm approach to ab initio protein folding. It does not focus on dihedral angles exclusively, but mainly operates on introduction, extension, break-up, and destruction of secondary structure elements, given as correlated dihedral angle values. In first test applications to polyalanines (up to 60 residues) and random primary sequences (up to 40 residues), we demonstrate that this use of prior knowledge is well balanced: On the one hand, it ensures quick introduction of secondary structure elements if they are favorable for a given primary sequence, but still allows for efficient location of pure random coil solutions without enforcing any secondary structure elements, if folds of this type are preferred by the given primary sequence. Furthermore, the algorithm is clearly able to pack several secondary structure elements into favorable tertiary structure arrangements, although no part of the algorithm is explicitly designed to do this. In first test examples on real-life peptides between 21 and 44 residues from the Protein Data Bank, the quality of the results depends on the force field used (as expected); nevertheless, we can show that the algorithm is able to find structures in good agreement with the targets easily and consistently, if the force field allows for that. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1169,1179, 2005 [source]


    Sexual Dimorphism in America: Geometric Morphometric Analysis of the Craniofacial Region,

    JOURNAL OF FORENSIC SCIENCES, Issue 1 2008
    Erin H. Kimmerle Ph.D.
    Abstract:, One of the four pillars of the anthropological protocol is the estimation of sex. The protocol generally consists of linear metric analysis or visually assessing individual skeletal traits on the skull and pelvis based on an ordinal scale of 1,5, ranging from very masculine to very feminine. The morphologic traits are then some how averaged by the investigator to estimate sex. Some skulls may be misclassified because of apparent morphologic features that appear more or less robust due to size differences among individuals. The question of misclassification may be further exemplified in light of comparisons across populations that may differ not only in cranial robusticity but also in stature and general physique. The purpose of this study is to further examine the effect of size and sex on craniofacial shape among American populations to better understand the allometric foundation of skeletal traits currently used for sex estimation. Three-dimensional coordinates of 16 standard craniofacial landmarks were collected using a Microscribe-3DX digitizer. Data were collected for 118 American White and Black males and females from the W.M. Bass Donated Collection and the Forensic Data Bank. The MANCOVA procedure tested shape differences as a function of sex and size. Sex had a significant influence on shape for both American Whites (F = 2.90; d.f. = 19, 39; p > F = 0.0024) and Blacks (F = 2.81; d.f. = 19, 37; p > F = 0.0035), whereas size did not have a significant influence on shape in either Whites (F = 1.69; d.f. = 19, 39; p > F = 0.08) or Blacks (F = 1.09; d.f. = 19, 37; p > F = 0.40). Therefore, for each sex, individuals of various sizes were statistically the same shape. In other words, while significant differences were present between the size of males and females (males on average were larger), there was no size effect beyond that accounted for by sex differences in size. Moreover, the consistency between American groups is interesting as it suggests that population differences in sexual dimorphism may result more from human variation in size than allometric variation in craniofacial morphology. [source]


    Analysis of a concept for predicting missing group interaction parameters of the UNIFAC model using connectivity indices

    AICHE JOURNAL, Issue 6 2009
    André Mohs
    Abstract The reliability of a method for the determination of missing group interaction parameters for the UNIFAC model1 proposed by Gani et al.2 was carefully examined. In this method, called CI-UNIFAC, the missing group interaction parameters are determined by means of connectivity indices. Such a method would be very desirable since it would save a lot of time and money spent for measuring VLE data to fill the gaps in the UNIFAC parameter matrix. Because of the great importance of distillation processes for the chemical industry mainly the results for vapor-liquid equilibria (VLE) were investigated using the data stored in the Dortmund Data Bank and VLE data measured. There are examples in which the method works quite well, but often the procedure leads to poor results. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source]


    Group contribution prediction of surface charge density profiles for COSMO-RS(Ol)

    AICHE JOURNAL, Issue 12 2007
    Tiancheng Mu
    Abstract A new method for predicting the surface charge density distribution (, profile) and cavity volume of molecules based on group contributions was developed. The original , profiles used for the regression were obtained using Gaussian 03 B3LYP/6-311G(d,p). In total 1363 , profiles were used for the regression of group parameters. Group definitions are identical to those used previously for boiling point estimation. Original and estimated , profiles were used to predict activity coefficients at infinite dilution and VLE data of binary systems using the COSMO-RS(Ol) model. The results were compared with the experimental data stored in the Dortmund Data Bank. In many cases the results were of comparable accuracy. However, for a few compounds, poor results were obtained, in particular for conjugated components like nitrobenzenes. The method offers a fast and reliable generation of , profiles to be used with COSMO-RS(Ol) within its range of applicability. © 2007 American Institute of Chemical Engineers AIChE J, 2007 [source]


    Prediction of phase equilibria and excess properties for systems with sulfones

    AICHE JOURNAL, Issue 2 2003
    Roland Wittig
    The group contribution method modified UNIFAC (Dortmund) has become very popular because of its broad applications, and reliable predictions for vapor-liquid equilibria, solid-liquid equilibria, liquid-liquid equilibria, activity coefficients at infinite dilution, azeotropic data and excess enthalpies in a wide temperature range. Therefore, the existing parameter matrix for the modified UNIFAC method is continuously extended with the help of the Dortmund Data Bank and by carrying out systematic measurements. The new main group for sulfones, such as that required to describe systems with the selective solvent sulfolane, is introduced, as well as ten new pairs of group interaction parameters for modified UNIFAC. [source]


    Local structure investigation of the active site of the imidazolonepropionase from Bacillus subtilis by XANES spectroscopy and ab initio calculations

    JOURNAL OF SYNCHROTRON RADIATION, Issue 2 2008
    Feifei Yang
    Imidazolonepropionase is an important enzyme that plays a crucial role in the degradation of the histidine in mammals and bacteria. In this contribution a detailed structural investigation is presented of the imidazolonepropionase from Bacillus subtilis at the zinc site by X-ray absorption near-edge structure (XANES) spectroscopy combining experimental data with ab initio calculation in the framework of the multiple-scattering theory. The resolved local structure leads to a modification of the data set in the Protein Data Bank (PDB) (PDB code 2BB0). Actually, data suggest that the carboxyl of the Asp324 moves far away from the zinc ion at the center, while the water molecule and the nearest-neighbor histidines move towards it. This new conformation and the occurrence of a short water-to-zinc bond length support the nucleophilic attack catalytic mechanism proposed for this enzyme. [source]


    The changing face of scientific discourse: Analysis of genomic and proteomic database usage and acceptance

    JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY, Issue 10 2003
    Cecelia Brown
    The explosion of the field of molecular biology is paralleled by the growth in usage and acceptance of Web-based genomic and proteomic databases (GPD) such as GenBank and Protein Data Bank in the scholarly communication of scientists. Surveys, case studies, analysis of bibliographic records from Medline and CAPlus, and examination of "Instructions to Authors" sections of molecular biology journals all confirm the integral role of GPD in the scientific literature cycle. Over the past 20 years the place of GPD in the culture of molecular biologists was observed to move from tacit implication to explicit knowledge. Originally journals suggested deposition of data in GDP but by the late1980s, the majority of journals mandated deposition of data for a manuscript to be accepted for publication. A surge subsequently occurred in the number of articles retrievable from Medline and CAPlus using the keyword "GenBank". GPD were not found to a new form of publication, but rather a fundamental storage and retrieval mechanism for vast amounts of molecular biology information that support the creation of scientific intellectual property. For science to continue to advance, scientists unequivocally agreed that GDP must remain free of peer-review and available at no charge to the public. The results suggest that the existing models of scientific communication should be updated to incorporate GDP data deposition into the current continuum of scientific communication. [source]


    Structures of the OmpF porin crystallized in the presence of foscholine-12

    PROTEIN SCIENCE, Issue 5 2010
    Georgia Kefala
    Abstract The endogenous Escherichia coli porin OmpF was crystallized as an accidental by-product of our efforts to express, purify, and crystallize the E. coli integral membrane protein KdpD in the presence of foscholine-12 (FC12). FC12 is widely used in membrane protein studies, but no crystal structure of a protein that was both purified and crystallized with this detergent has been reported in the Protein Data Bank. Crystallization screening for KdpD yielded two different crystals of contaminating protein OmpF. Here, we report two OmpF structures, the first membrane protein crystal structures for which extraction, purification, and crystallization were done exclusively with FC12. The first structure was refined in space group P21 with cell parameters a = 136.7 Ĺ, b = 210.5 Ĺ, c = 137 Ĺ, and , = 100.5°, and the resolution of 3.8 Ĺ. The second structure was solved at the resolution of 4.4 Ĺ and was refined in the P321 space group, with unit cell parameters a = 215.5 Ĺ, b = 215.5 Ĺ, c = 137.5 Ĺ, and , = 120°. Both crystal forms show novel crystal packing, in which the building block is a tetrahedral arrangement of four trimers. Additionally, we discuss the use of FC12 for membrane protein crystallization and structure determination, as well as the problem of the OmpF contamination for membrane proteins overexpressed in E. coli. [source]


    Quantitative prediction of protein,protein binding affinity with a potential of mean force considering volume correction

    PROTEIN SCIENCE, Issue 12 2009
    Yu Su
    Abstract Quantitative prediction of protein,protein binding affinity is essential for understanding protein,protein interactions. In this article, an atomic level potential of mean force (PMF) considering volume correction is presented for the prediction of protein,protein binding affinity. The potential is obtained by statistically analyzing X-ray structures of protein,protein complexes in the Protein Data Bank. This approach circumvents the complicated steps of the volume correction process and is very easy to implement in practice. It can obtain more reasonable pair potential compared with traditional PMF and shows a classic picture of nonbonded atom pair interaction as Lennard-Jones potential. To evaluate the prediction ability for protein,protein binding affinity, six test sets are examined. Sets 1,5 were used as test set in five published studies, respectively, and set 6 was the union set of sets 1,5, with a total of 86 protein,protein complexes. The correlation coefficient (R) and standard deviation (SD) of fitting predicted affinity to experimental data were calculated to compare the performance of ours with that in literature. Our predictions on sets 1,5 were as good as the best prediction reported in the published studies, and for union set 6, R = 0.76, SD = 2.24 kcal/mol. Furthermore, we found that the volume correction can significantly improve the prediction ability. This approach can also promote the research on docking and protein structure prediction. [source]


    Identification of transient hub proteins and the possible structural basis for their multiple interactions

    PROTEIN SCIENCE, Issue 1 2008
    Miho Higurashi
    Abstract Proteins that can interact with multiple partners play central roles in the network of protein,protein interactions. They are called hub proteins, and recently it was suggested that an abundance of intrinsically disordered regions on their surfaces facilitates their binding to multiple partners. However, in those studies, the hub proteins were identified as proteins with multiple partners, regardless of whether the interactions were transient or permanent. As a result, a certain number of hub proteins are subunits of stable multi-subunit proteins, such as supramolecules. It is well known that stable complexes and transient complexes have different structural features, and thus the statistics based on the current definition of hub proteins will hide the true nature of hub proteins. Therefore, in this paper, we first describe a new approach to identify proteins with multiple partners dynamically, using the Protein Data Bank, and then we performed statistical analyses of the structural features of these proteins. We refer to the proteins as transient hub proteins or sociable proteins, to clarify the difference with hub proteins. As a result, we found that the main difference between sociable and nonsociable proteins is not the abundance of disordered regions, in contrast to the previous studies, but rather the structural flexibility of the entire protein. We also found greater predominance of charged and polar residues in sociable proteins than previously reported. [source]


    Models of S/, interactions in protein structures: Comparison of the H2S,benzene complex with PDB data

    PROTEIN SCIENCE, Issue 10 2007
    Ashley L. Ringer
    Abstract S/, interactions are prevalent in biochemistry and play an important role in protein folding and stabilization. Geometries of cysteine/aromatic interactions found in crystal structures from the Brookhaven Protein Data Bank (PDB) are analyzed and compared with the equilibrium configurations predicted by high-level quantum mechanical results for the H2S,benzene complex. A correlation is observed between the energetically favorable configurations on the quantum mechanical potential energy surface of the H2S,benzene model and the cysteine/aromatic configurations most frequently found in crystal structures of the PDB. In contrast to some previous PDB analyses, configurations with the sulfur over the aromatic ring are found to be the most important. Our results suggest that accurate quantum computations on models of noncovalent interactions may be helpful in understanding the structures of proteins and other complex systems. [source]


    The long-range electrostatic interactions control tRNA,aminoacyl-tRNA synthetase complex formation

    PROTEIN SCIENCE, Issue 6 2003
    Dmitry Tworowski
    3D, three-dimensional; PDB, Protein Data Bank of experimentally determined 3D structures of proteins; aaRS, aminoacyl-tRNA synthetase Abstract In most cases aminoacyl-tRNA synthetases (aaRSs) are negatively charged, as are the tRNA substrates. It is apparent that there are driving forces that provide a long-range attraction between like charge aaRS and tRNA, and ensure formation of "close encounters." Based on numerical solutions to the nonlinear Poisson-Boltzmann equation, we evaluated the electrostatic potential generated by different aaRSs. The 3D-isopotential surfaces calculated for different aaRSs at 0.01 kT/e contour level reveal the presence of large positive patches,one patch for each tRNA molecule. This is true for classes I and II monomers, dimers, and heterotetramers. The potential maps keep their characteristic features over a wide range of contour levels. The results suggest that nonspecific electrostatic interactions are the driving forces of primary stickiness of aaRSs,tRNA complexes. The long-range attraction in aaRS,tRNA systems is explained by capture of negatively charged tRNA into "blue space area" of the positive potential generated by aaRSs. Localization of tRNA in this area is a prerequisite for overcoming the barrier of Brownian motion. [source]


    Simultaneous assignment and structure determination of a membrane protein from NMR orientational restraints

    PROTEIN SCIENCE, Issue 3 2003
    Francesca M. Marassi
    Abstract A solid-state NMR approach for simultaneous resonance assignment and three-dimensional structure determination of a membrane protein in lipid bilayers is described. The approach is based on the scattering, hence the descriptor "shotgun," of 15N-labeled amino acids throughout the protein sequence (and the resulting NMR spectra). The samples are obtained by protein expression in bacteria grown on media in which one type of amino acid is labeled and the others are not. Shotgun NMR short-circuits the laborious and time-consuming process of obtaining complete sequential assignments prior to the calculation of a protein structure from the NMR data by taking advantage of the orientational information inherent to the spectra of aligned proteins. As a result, it is possible to simultaneously assign resonances and measure orientational restraints for structure determination. A total of five two-dimensional 1H/15N PISEMA (polarization inversion spin exchange at the magic angle) spectra, from one uniformly and four selectively 15N-labeled samples, were sufficient to determine the structure of the membrane-bound form of the 50-residue major pVIII coat protein of fd filamentous bacteriophage. Pisa (polarity index slat angle) wheels are an essential element in the process, which starts with the simultaneous assignment of resonances and the assembly of isolated polypeptide segments, and culminates in the complete three-dimensional structure of the protein with atomic resolution. The principles are also applicable to weakly aligned proteins studied by solution NMR spectroscopy. [The structure we determined for the membrane-bound form of the Fd bacteriophage pVIII coat protein has been deposited in the Protein Data Bank as PDB file 1MZT.] [source]


    Long membrane helices and short loops predicted less accurately

    PROTEIN SCIENCE, Issue 12 2002
    Chien Peter Chen
    3D, three-dimensional; DSSP, program assigning secondary structure (Kabsch and Sander 1983); HMM, hidden Markov model; PDB, Protein Data Bank of experimentally determined 3D structures of proteins (Bernstein et al. 1977; Berman et al. 2000); SWISS-PROT, database of protein sequences (Bairoch and Apweiler 2000); TM, transmembrane; TMH, transmembrane helix Abstract Low-resolution experiments suggest that most membrane helices span over 17,25 residues and that most loops between two helices are longer than 15 residues. Both constraints have been used explicitly in the development of prediction methods. Here, we compared the largest possible sequence,unique data sets from high- and low-resolution experiments. For the high-resolution data, we found that only half of the helices fall into the expected length interval and that half of the loops were shorter than 10 residues. We compared the accuracy of detecting short loops and long helices for 28 advanced and simple prediction methods: All methods predicted short loops less accurately than longer ones. In particular, loops shorter than 7 residues appeared to be very difficult to detect by current methods. Similarly, all methods tended to be more accurate for longer than for shorter helices. However, helices with more than 32 residues were predicted less accurately than all other helices. Our findings may suggest particular strategies for improving predictions of membrane helices. [source]


    Protein stability indicates divergent evolution of PD-(D/E)XK type II restriction endonucleases

    PROTEIN SCIENCE, Issue 8 2002
    Monika Fuxreiter
    SC, stabilization center; PDB, Protein Data Bank Abstract Type II restriction endonucleases recognize 4,8 base-pair-long DNA sequences and catalyze their cleavage with remarkable specificity. Crystal structures of the PD-(DE)XK superfamily revealed a common ,/, core motif and similar active site. In contrast, these enzymes show little sequence similarity and use different strategies to interact with their substrate DNA. The intriguing question is whether this enzyme family could have evolved from a common origin. In our present work, protein structure stability elements were analyzed and compared in three parts of PD-(DE)XK type II restriction endonucleases: (1) core motif, (2) active-site residues, and (3) residues playing role in DNA recognition. High correlation was found between the active-site residues and those stabilization factors that contribute to preventing structural decay. DNA recognition sites were also observed to participate in stabilization centers. It indicates that recognition motifs and active sites in PD-(DE)XK type II restriction endonucleases should have been evolutionary more conserved than other parts of the structure. Based on this observation it is proposed that PD-(DE)XK type II restriction endonucleases have developed from a common ancestor with divergent evolution. [source]


    Soft protein,protein docking in internal coordinates

    PROTEIN SCIENCE, Issue 2 2002
    Juan Fernández-Recio
    PDB, Protein Data Bank; ICM, Internal Coordinate Mechanics; RMSD, root-mean-square deviation Abstract The association of two biological macromolecules is a fundamental biological phenomenon and an unsolved theoretical problem. Docking methods for ab initio prediction of association of two independently determined protein structures usually fail when they are applied to a large set of complexes, mostly because of inaccuracies in the scoring function and/or difficulties on simulating the rearrangement of the interface residues on binding. In this work we present an efficient pseudo-Brownian rigid-body docking procedure followed by Biased Probability Monte Carlo Minimization of the ligand interacting side-chains. The use of a soft interaction energy function precalculated on a grid, instead of the explicit energy, drastically increased the speed of the procedure. The method was tested on a benchmark of 24 protein,protein complexes in which the three-dimensional structures of their subunits (bound and free) were available. The rank of the near-native conformation in a list of candidate docking solutions was <20 in 85% of complexes with no major backbone motion on binding. Among them, as many as 7 out of 11 (64%) protease-inhibitor complexes can be successfully predicted as the highest rank conformations. The presented method can be further refined to include the binding site predictions and applied to the structures generated by the structural proteomics projects. All scripts are available on the Web. [source]


    A multimethod study of needs for physician assessment: Implications for education and regulation

    THE JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS, Issue 4 2009
    Richard Hawkins MD Senior Vice President for Professional, Scientific Affairs
    Abstract Introduction: Deficiencies in physician competence play an important role in medical errors and poor-quality health care. National trends toward implementation of continuous assessment of physicians hold potential for significant impact on patient care because minor deficiencies can be identified before patient safety is threatened. However, the availability of assessment methods and the quality of existing tools vary, and a better understanding of the types of deficiencies seen in physicians is required to prioritize the development and enhancement of assessment and remediation methods. Methods: Surveys of physicians and licensing authorities and analysis of the Federation of State Medical Boards (FSMB) Board Action Data Bank were used to collect information describing the nature and types of problems seen in practicing physicians. Focus groups, depth interviews with key professional stakeholders, and state medical board site visits provided additional information about deficiencies in physician competence. Results: Quantitative and qualitative analyses identified (1) communication skills as a priority target for assessment approaches that also should focus on professional behaviors, knowledge, clinical judgment, and health-care quality; and (2) differences between regulatory approaches of licensing and certifying bodies contribute to a culture that limits effective self-assessment and continuous quality improvement. System problems impacting physician performance emerged as an important theme in the qualitative analysis. Discussion: Considering alternative perspectives from the regulatory, education, and practice communities helps to define assessment priorities for physicians, facilitating development of a coherent and defensible approach to assessment and continuing professional development that promises to provide a more comprehensive solution to problems of health-care quality in the United States. [source]


    Effect of Race and Insurance on Outcome of Pediatric Trauma

    ACADEMIC EMERGENCY MEDICINE, Issue 8 2010
    Wael Hakmeh DO
    ACADEMIC EMERGENCY MEDICINE 2010; 17:809,812 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, This study sought to determine if insurance or race status affect trauma outcomes in pediatric trauma patients. Methods:, Using the National Trauma Data Bank (NTDB; v6.2), the following variables were extracted: age (0,17 years), payment type (insured, Medicaid/Medicare, or self-pay), race (white, Black/African American, or Hispanic), Injury Severity Score (ISS > 8), type of trauma (blunt or penetrating), and discharge status (alive or dead). Data were analyzed using logistic regression. Results:, Of the 70,781 patient visits analyzed, 67% were insured, 23% were Medicaid/Medicare, and 10% were self-pay. Self-pay patients had higher mortality (11%, compared to Medicaid/Medicare at 5% and insured at 4%; p < 0.001). African Americans and Hispanics also had higher mortality (7 and 6%) compared to whites (4%; p < 0.001). Self-pay patients more likely suffered penetrating trauma than insured patients (12% vs. 4%; p < 0.001), and mortality for penetrating trauma self-pay patients was 29%, compared to only 11% for penetrating trauma insured patients (p < 0.001). The mortality rate varied from a low of 3% for insured whites, to 18% for self-pay African Americans. Logistic regression (including race, insurance status, injury type, and ISS) revealed that African Americans and Hispanics both had an increased risk of death compared to whites (African American odds ratio [OR] = 1.37, Hispanic OR = 1.20). Medicaid/Medicare patients had a slightly increased risk of death with OR = 1.14, but self-pay patients were almost three times more likely to die (adjusted OR = 2.92). Conclusions:, After controlling for ISS and type of injury, mortality disparity exists for uninsured, African American, and Hispanic pediatric trauma patients. Although the reasons for this are unclear, efforts to decrease these disparities are needed. [source]


    The Impact of Injury Coding Schemes on Predicting Hospital Mortality After Pediatric Injury

    ACADEMIC EMERGENCY MEDICINE, Issue 7 2009
    Randall S. Burd MD
    Abstract Objectives:, Accurate adjustment for injury severity is needed to evaluate the effectiveness of trauma management. While the choice of injury coding scheme used for modeling affects performance, the impact of combining coding schemes on performance has not been evaluated. The purpose of this study was to use Bayesian logistic regression to develop models predicting hospital mortality in injured children and to compare the performance of models developed using different injury coding schemes. Methods:, Records of children (age < 15 years) admitted after injury were obtained from the National Trauma Data Bank (NTDB) and the National Pediatric Trauma Registry (NPTR) and used to train Bayesian logistic regression models predicting mortality using three injury coding schemes (International Classification of Disease-9th revision [ICD-9] injury codes, the Abbreviated Injury Scale [AIS] severity scores, and the Barell matrix) and their combinations. Model performance was evaluated using independent data from the NTDB and the Kids' Inpatient Database 2003 (KID). Results:, Discrimination was optimal when modeling both ICD-9 and AIS severity codes (area under the receiver operating curve [AUC] = 0.921 [NTDB] and 0.967 [KID], Hosmer-Lemeshow [HL] h-statistic = 115 [NTDB] and 147 [KID]), while calibration was optimal when modeling coding based on the Barell matrix (AUC = 0.882 [NTDB] and 0.936 [KID], HL h-statistic = 19 [NTDB] and 69 [KID]). When compared to models based on ICD-9 codes alone, models that also included AIS severity scores and coding from the Barell matrix showed improved discrimination and calibration. Conclusions:, Mortality models that incorporate additional injury coding schemes perform better than those based on ICD-9 codes alone in the setting of pediatric trauma. Combining injury coding schemes may be an effective approach for improving the predictive performance of empirically derived estimates of injury mortality. [source]


    Detection and correction of underassigned rotational symmetry prior to structure deposition

    ACTA CRYSTALLOGRAPHICA SECTION D, Issue 5 2010
    Billy K. Poon
    Up to 2% of X-ray structures in the Protein Data Bank (PDB) potentially fit into a higher symmetry space group. Redundant protein chains in these structures can be made compatible with exact crystallographic symmetry with minimal atomic movements that are smaller than the expected range of coordinate uncertainty. The incidence of problem cases is somewhat difficult to define precisely, as there is no clear line between underassigned symmetry, in which the subunit differences are unsupported by the data, and pseudosymmetry, in which the subunit differences rest on small but significant intensity differences in the diffraction pattern. To help catch symmetry-assignment problems in the future, it is useful to add a validation step that operates on the refined coordinates just prior to structure deposition. If redundant symmetry-related chains can be removed at this stage, the resulting model (in a higher symmetry space group) can readily serve as an isomorphous replacement starting point for re-refinement using re-indexed and re-integrated raw data. These ideas are implemented in new software tools available at http://cci.lbl.gov/labelit. [source]