PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Protein structure”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1995

Characterizing oriented protein structural sites using biochemical properties.

A protein site is a region of a three-dimensional protein structure with a distinguishing functional or structural role. Certain sites recur in different protein structures (for example catalytic sites, calcium binding sites, and some types of turns), but maintain critical shared features. To facilitate the analysis of such protein sites, we have developed a computer system for analyzing the spatial distributions of biochemical properties around a site. The system takes a set of similar sites and a set of control nonsites, and finds differences between them. Specifically, it compares distributions of the properties surrounding the sites with those surrounding the nonsites, and reports statistically significant differences. In this paper, we use our method to analyze the features in the active site of the serine protease enzymes. We compare the use of radial distributions (shells) with 3-D grids (blocks) in the analysis of the active site. We demonstrate three different strategies for focusing attention on significant findings, based on properties of interest, spatial volumes of interest, and on the level of statistical significance. Finally, we show that the program automatically identifies conserved sequential, secondary structural and biophysical features of the serine protease active site, using noncatalytic histidine residues as a control environment.

Algorithms↗
PubMedDate not supplied

[Statistical distribution of dipeptides in protein structures and dynamic characteristics of some protein fragments].

Statistical distributions of the occurrence of dipeptide fragments in proteins were studied. Various algorithms of ordering of files of frequency distribution were used. A correlation of occurrence of pairs of amino acid residues in various classes of proteins was established. The problem of the dynamic compatibility of amino acid residues in protein structures is discussed. The dynamic properties of frequently and seldom occurring dimers of amino acids are compared.

Amino Acid Sequence↗
PubMed1991

Construction of intertypic chimeric dengue viruses by substitution of structural protein genes.

Dengue virus contains an 11-kilobase positive-strand RNA genome that codes for, in one open reading frame, three structural proteins (capsid, premembrane, and envelope), followed by seven nonstructural proteins. The structural protein genes of a full-length cDNA clone of type 4 dengue virus were replaced with the corresponding genes of dengue 1 or dengue 2 to create intertypic chimeric cDNA. The RNA transcripts made from these templates were infectious when transfected into permissive cells in culture. Progeny of chimeric cDNA produced apparently authentic dengue 1 or dengue 2 structural proteins, together with dengue 4 nonstructural proteins, and as a consequence exhibited type 1 or type 2 serological specificity. Both of the chimeras ultimately grew to the same titer as their type 1 or type 2 parent, but the type 2/type 4 chimera grew very slowly. This chimera also produced small plaques; in contrast, the type 1/type 4 chimera produced normal size plaques. The type 2/type 4 chimera retained the mouse neurovirulence of the dengue 2 virus, which was the source of its structural protein genes. Each of the mice inoculated intracerebrally with the chimera died, but survival time was prolonged. The retardation of replication of the type 2/type 4 chimeric virus suggests that this virus and possibly other intertypic dengue virus chimeras with similar properties should be examined for attenuation in primates and possible usefulness in a live dengue virus vaccine for humans.

Animals↗
PubMed2005

Protein structure prediction: inroads to biology.

In recent years, there has been significant progress in the ability to predict the three-dimensional structure of proteins from their amino acid sequence. Progress has been due to new methods to extract the growing amount of information in sequence and structure databases and improved computational descriptions of protein energetics. This review summarizes recent advances in these areas and describes a number of novel biological applications made possible by structure prediction. Despite remaining challenges, protein structure prediction is becoming an extremely useful tool in understanding phenomena in modern molecular and cell biology.

Algorithms↗
PubMed2001

FlexE: efficient molecular docking considering protein structure variations.

Side-chain or even backbone adjustments upon docking of different ligands to the same protein structure, a phenomenon known as induced fit, are frequently observed. Sometimes point mutations within the active site influence the ligand binding of proteins. Furthermore, for homology derived protein structures there are often ambiguities in side-chain placement and uncertainties in loop modeling which may be critical for docking applications. Nevertheless, only very few molecular docking approaches have taken into account such variations in protein structures. We present the new software tool FlexE which addresses the problem of protein structure variations during docking calculations. FlexE can dock flexible ligands into an ensemble of protein structures which represents the flexibility, point mutations, or alternative models of a protein. The FlexE approach is based on a united protein description generated from the superimposed structures of the ensemble. For varying parts of the protein, discrete alternative conformations are explicitly taken into account, which can be combinatorially joined to create new valid protein structures.FlexE was evaluated using ten protein structure ensembles containing 105 crystal structures from the PDB and one modeled structure with 60 ligands in total. For 50 ligands (83 %) FlexE finds a placement with an RMSD to the crystal structure below 2.0 A. In all cases our results are of similar quality to the best solution obtained by sequentially docking the ligands into all protein structures (cross docking). In most cases the computing time is significantly lower than the accumulated run times for the single structures. FlexE takes about five and a half minutes on average for placing one ligand into the united protein description on a common workstation. The example of the aldose reductase demonstrates the necessity of considering protein structure variations for docking calculations. We docked three potent inhibitors into four protein structures with substantial conformational changes within the active site. Using only one rigid protein structure for screening would have missed potential inhibitors whereas all inhibitors can be docked taking all protein structures into account.

Aldehyde Reductase↗
PubMed2000

Anatomy of protein structures: visualizing how a one-dimensional protein chain folds into a three-dimensional shape.

Here, we depict the anatomy of protein structures in terms of the protein folding process. Via an iterative, top-down dissecting procedure, tertiary structures are spliced down to reveal their anatomy: first, to produce domains (defined by visual three-dimensional inspection criteria); then, hydrophobic folding units (HFU); and, at the end of a multilevel process, a set of building blocks. The resulting anatomy tree organization not only clearly depicts the organization of a one-dimensional polypeptide chain in three-dimensional space but also straightforwardly describes the most likely folding pathway(s). Comparison of the tree with the formation of the hydrophobic folding units through combinatorial assembly of the building blocks illustrates how the chain folds in a sequential or a complex folding pathway. Further, the tree points to the kinetics of the folding, whether the chain is a fast or a slow folder, and the probability of misfolding. Our ability to successfully dissect the protein into an anatomy tree illustrates that protein folding is a hierarchical process and further validates a building blocks protein folding model.

Actins↗
PubMed2002

A hypergraph-based method for unification of existing protein structure- and sequence-families.

Classification of proteins is a major challenge in bioinformatics. Here an approach is presented, that unifies different existing classifications of protein structures and sequences. Protein structural domains are represented as nodes in a hypergraph. Shared memberships in sequence families result in hyperedges in the graph. The presented method partitions the hypergraph into clusters of structural domains. Each computed cluster is based on a set of shared sequence family memberships. Thus, the clusters put existing protein sequence families into the context of structural family hierarchies. Conversely, structural domains are related to their sequence family memberships, which can be used to gain further knowledge about the respective structural families.

Databases, Protein↗
PubMed2006

Application of the use of high-throughput technologies to the determination of protein structures of bacterial and viral pathogens.

The Structural Proteomics In Europe (SPINE) programme is aimed at the development and implementation of high-throughput technologies for the efficient structure determination of proteins of biomedical importance, such as those of bacterial and viral pathogens linked to human health. Despite the challenging nature of some of these targets, 175 novel pathogen protein structures (approximately 220 including complexes) have been determined to date. Here the impact of several technologies on the structural determination of proteins from human pathogens is illustrated with selected examples, including the parallel expression of multiple constructs, the use of standardized refolding protocols and optimized crystallization screens.

Animals↗
PubMed2004

Pairwise protein structure alignment based on an orientation-independent backbone representation.

Determining structural similarities between proteins is an important problem since it can help identify functional and evolutionary relationships. In this paper, an algorithm is proposed to align two protein structures. Given the protein backbones, the algorithm finds a rigid motion of one backbone onto the other such that large substructures are matched. The algorithm uses a representation of the backbones that is independent of their relative orientations in space and applies dynamic programming to this representation to compute an initial alignment, which is then refined iteratively. Experiments indicate that the algorithm is competitive with two well-known algorithms, namely DALI and LOCK.

Algorithms↗
PubMed1997

The effect of denaturants on protein structure.

Virtually all studies of the protein-folding reaction add either heat, acid, or a chemical denaturant to an aqueous protein solution in order to perturb the protein structure. When chemical denaturants are used, very high concentrations are usually necessary to observe any change in protein structure. In a solution with such high denaturant concentrations, both the structure of the protein and the structure of the solvent around the protein can be altered. X-ray crystallography is the obvious experimental technique to probe both types of changes. In this paper, we report the crystal structures of dihydrofolate reductase with urea and of ribonuclease A with guanidinium chloride. These two classic denaturants have similar effects on the native structure of the protein. The most important change that occurs is a reduction in the overall thermal factor. These structures offer a molecular explanation for the reduction in mobility. Although the reduction is observed only with the native enzyme in the crystal, a similar decrease in mobility has also been observed in the unfolded state in solution (Makhatadze G, Privalov PL. 1992. Protein interactions with urea and guanidinium chloride: A calorimetric study.

Crystallography, X-Ray↗
PubMed2004

Structural exon database, SEDB, mapping exon boundaries on multiple protein structures.

UNLABELLED: Comparative analysis of exon/intron organization of genes and their resulting protein structures is important for understanding evolutionary relationships between species, rules of protein organization and protein functionality. We present Structural Exon Database (SEDB), with a Web interface, an application that allows users to retrieve the exon/intron organization of genes and map the location of the exon boundaries and the intron phase onto a multiple structural alignment. SEDB is linked with Friend, an integrated analytical multiple sequence/structure viewer, which allows simultaneous visualization of exon boundaries on structure and sequence alignments. With SEDB researchers can study the correlations of gene structure with the properties of the encoded three-dimensional protein structures across eukaryotic organisms. AVAILABILITY: SEDB is publicly available at http://glinka.bio.neu.edu/SEDB/SEDB.html SUPPLEMENTARY INFORMATION: On the SEDB Web site.

Databases, Genetic↗
PubMed2000

Protein structure alignment using environmental profiles.

A new protein structure alignment procedure is described. An initial alignment is made by comparing a one-dimensional list of primary, secondary and tertiary structural features (profiles) of two proteins, without explicitly considering the three-dimensional geometry of the structures. The alignment is then iteratively refined in the second step, in which new alignments are found by three-dimensional superposition of the structures based on the current alignment. This new procedure is fast enough to do all-against-all structural comparisons routinely. The procedure sometimes finds an alignment that suggests an evolutionary relationship and which is not normally obtained if only geometry is considered. All pair-wise comparisons were made among 3539 protein structural domains that represent all known protein structures. The resulting 3539 z-scores were used to cluster the proteins. The number of main clusters increased continuously as the z-cutoff was raised, but the number of multiple-member clusters showed a maximum at z-cutoff values of 5.0 and 5.5. When a z-cutoff value of 5.0 was used, the total number of main clusters was 2043, of which only 336 clusters had more than one member.

Amino Acid Sequence↗
PubMed1998

Regression analysis of multiple protein structures.

A general framework is presented for analyzing multiple protein structures using statistical regression methods. The regression approach can superimpose protein structures rigidly or with shear. Also, this approach can superimpose multiple structures explicitly, without resorting to pairwise superpositions. The algorithm alternates between matching corresponding landmarks among the protein structures and superimposing these landmarks. Matching is performed using a robust dynamic programming technique that uses gap penalties that adapt to the given data. Superposition is performed using either orthogonal transformations, which impose the rigid-body assumption, or affine transformations, which allow shear. The resulting regression model of a protein family measures the amount of structural variability at each landmark. A variation of our algorithm permits a separate weight for each landmark, thereby allowing one to emphasize particular segments of a protein structure or to compensate for variances that differ at various positions in a structure. In addition, a method is introduced for finding an initial correspondence, by measuring the discrete curvature along each protein backbone. Discrete curvature also characterizes the secondary structure of a protein backbone, distinguishing among helical, strand, and loop regions. An example is presented involving a set of seven globin structures. Regression analysis, using both affine and orthogonal transformations, reveals that globins are most strongly conserved structurally in helical regions, particularly in the mid-regions of the E, F, and G helices.

Algorithms↗
PubMed1997

Visible volume: a robust measure for protein structure characterization.

We propose a new characterization of protein structure based on the natural tetrahedral geometry of the beta-carbon and a new geometric measure of structural similarity, called visible volume. In our model, the side-chains are replaced by an ideal tetrahedron, the orientation of which is fixed with respect to the backbone and corresponds to the preferred rotamer directions. Visible volume is a measure of the non-occluded empty space surrounding each residue position after the side-chains have been removed. It is a robust, parameter-free, locally computed quantity that accounts for many of the spatial constraints that are of relevance to the corresponding position in the native structure. When computing visible volume, we ignore the nature of both the residue observed at each side and the ones surrounding it. We focus instead on the space that, together, these residues could occupy. By doing so, we are able to quantify a new kind of invariance beyond the apparent variations within protein families, namely, the conservation of the physical space available at structurally equivalent positions for side-chain packing. Corresponding positions in native structures are likely to be of interest in protein structure prediction, protein design, and homology modeling. Visible volume is related to the degree of exposure of a residue position and to the actual rotamers in native proteins. Here, we discuss the properties of this new measure, namely, its robustness with respect to both crystallographic uncertainties and naturally occurring variations in atomic coordinates, and the remarkable fact that it is essentially independent of the choice of the parameters used in calculating it. We also show how visible volume can be used to align protein structures, to identify structurally equivalent positions that are conserved in a family of proteins, and to single out positions in a protein that are likely to be of biological interest. These properties qualify visible volume as a powerful tool in a variety of applications, from the detailed analysis of protein structure to homology modeling, protein structural alignment, and the definition of better scoring functions for threading purposes.

Animals↗
PubMed2004

Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions.

The present paper describes the SSM algorithm of protein structure comparison in three dimensions, which includes an original procedure of matching graphs built on the protein's secondary-structure elements, followed by an iterative three-dimensional alignment of protein backbone Calpha atoms. The SSM results are compared with those obtained from other protein comparison servers, and the advantages and disadvantages of different scores that are used for structure recognition are discussed. A new score, balancing the r.m.s.d. and alignment length Nalign, is proposed. It is found that different servers agree reasonably well on the new score, while showing considerable differences in r.m.s.d. and Nalign.

Algorithms↗
PubMed2002

From information management to protein annotation: preparing protein structures for drug discovery.

In contrast to academic pursuits of structural genomics, Structural GenomiX (SGX) solves protein structures at high throughput for the main purpose of enhancing drug-discovery projects, either internally or in partnership with pharmaceutical/biotechnology companies. This involves a radical redesign of the pipeline of methods that turn a gene sequence into a three-dimensional protein structure. The various processes all report electronically to a Laboratory Information Management System (LIMS) to make sure all the parameters of the experiment are recorded in an accessible and 'mineable' form, helping guarantee reproducibility of results. Quality control at several key points keeps the process from branching out on a wrong hypothesis. Protein annotation, in a broad sense, takes care of the interpretation of a protein crystal structure or the crystal structure of one or several protein-ligand complexes. This interpretation both gathers all necessary biological information (protein function, mechanism, specific features within a protein family etc.) and hands over this information in a form accessible to medicinal chemistry teams designing specific small-molecule agonists or antagonists.

Crystallization↗
PubMed2006

Optimal isotope labelling for NMR protein structure determinations.

Nuclear-magnetic-resonance spectroscopy can determine the three-dimensional structure of proteins in solution. However, its potential has been limited by the difficulty of interpreting NMR spectra in the presence of broadened and overlapping resonance lines and low signal-to-noise ratios. Here we present stereo-array isotope labelling (SAIL), a technique that can overcome many of these problems by applying a complete stereospecific and regiospecific pattern of stable isotopes that is optimal with regard to the quality and information content of the resulting NMR spectra. SAIL uses exclusively chemically and enzymatically synthesized amino acids for cell-free protein expression. We demonstrate for the 17-kDa protein calmodulin and the 41-kDa maltodextrin-binding protein that SAIL offers sharpened lines, spectral simplification without loss of information, and the ability to rapidly collect the structural restraints required to solve a high-quality solution structure for proteins twice as large as commonly solved by NMR. It thus makes a large class of proteins newly accessible to detailed solution structure determination.

Amino Acids↗