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Structural Databases (structural + databases)
Selected AbstractsMercury CSD 2.0, new features for the visualization and investigation of crystal structuresJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 2 2008Clare F. Macrae The program Mercury, developed by the Cambridge Crystallographic Data Centre, is designed primarily as a crystal structure visualization tool. A new module of functionality has been produced, called the Materials Module, which allows highly customizable searching of structural databases for intermolecular interaction motifs and packing patterns. This new module also includes the ability to perform packing similarity calculations between structures containing the same compound. In addition to the Materials Module, a range of further enhancements to Mercury has been added in this latest release, including void visualization and links to ConQuest, Mogul and IsoStar. [source] Identifying native-like protein structures using physics-based potentialsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2002Brian N. Dominy Abstract As the field of structural genomics matures, new methods will be required that can accurately and rapidly distinguish reliable structure predictions from those that are more dubious. We present a method based on the CHARMM gas phase implicit hydrogen force field in conjunction with a generalized Born implicit solvation term that allows one to make such discrimination. We begin by analyzing pairs of threaded structures from the EMBL database, and find that it is possible to identify the misfolded structures with over 90% accuracy. Further, we find that misfolded states are generally favored by the solvation term due to the mispairing of favorable intramolecular ionic contacts. We also examine 29 sets of 29 misfolded globin sequences from Levitt's "Decoys ,R' Us" database generated using a sequence homology-based method. Again, we find that discrimination is possible with approximately 90% accuracy. Also, even in these less distorted structures, mispairing of ionic contacts results in a more favorable solvation energy for misfolded states. This is also found to be the case for collapsed, partially folded conformations of CspA and protein G taken from folding free energy calculations. We also find that the inclusion of the generalized Born solvation term, in postprocess energy evaluation, improves the correlation between structural similarity and energy in the globin database. This significantly improves the reliability of the hypothesis that more energetically favorable structures are also more similar to the native conformation. Additionally, we examine seven extensive collections of misfolded structures created by Park and Levitt using a four-state reduced model also contained in the "Decoys ,R' Us" database. Results from these large databases confirm those obtained in the EMBL and misfolded globin databases concerning predictive accuracy, the energetic advantage of misfolded proteins regarding the solvation component, and the improved correlation between energy and structural similarity due to implicit solvation. Z-scores computed for these databases are improved by including the generalized Born implicit solvation term, and are found to be comparable to trained and knowledge-based scoring functions. Finally, we briefly explore the dynamic behavior of a misfolded protein relative to properly folded conformations. We demonstrate that the misfolded conformation diverges quickly from its initial structure while the properly folded states remain stable. Proteins in this study are shown to be more stable than their misfolded counterparts and readily identified based on energetic as well as dynamic criteria. In summary, we demonstrate the utility of physics-based force fields in identifying native-like conformations in a variety of preconstructed structural databases. The details of this discrimination are shown to be dependent on the construction of the structural database. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 147,160, 2002 [source] Database searching by flexible protein structure alignmentPROTEIN SCIENCE, Issue 7 2004Yuzhen Ye Abstract We have recently developed a flexible protein structure alignment program (FATCAT) that identifies structural similarity, at the same time accounting for flexibility of protein structures. One of the most important applications of a structure alignment method is to aid in functional annotations by identifying similar structures in large structural databases. However, none of the flexible structure alignment methods were applied in this task because of a lack of significance estimation of flexible alignments. In this paper, we developed an estimate of the statistical significance of FATCAT alignment score, allowing us to use it as a database-searching tool. The results reported here show that (1) the distribution of the similarity score of FATCAT alignment between two unrelated protein structures follows the extreme value distribution (EVD), adding one more example to the current collection of EVDs of sequence and structure similarities; (2) introducing flexibility into structure comparison only slightly influences the sensitivity and specificity of identifying similar structures; and (3) the overall performance of FATCAT as a database searching tool is comparable to that of the widely used rigid-body structure comparison programs DALI and CE. Two examples illustrating the advantages of using flexible structure alignments in database searching are also presented. The conformational flexibilities that were detected in the first example may be involved with substrate specificity, and the conformational flexibilities detected in the second example may reflect the evolution of structures by block building. [source] Crystallographic model quality at a glanceACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2009Ludmila Urzhumtseva A crystallographic macromolecular model is typically characterized by a list of quality criteria, such as R factors, deviations from ideal stereochemistry and average B factors, which are usually provided as tables in publications or in structural databases. In order to facilitate a quick model-quality evaluation, a graphical representation is proposed. Each key parameter such as R factor or bond-length deviation from `ideal values' is shown graphically as a point on a `ruler'. These rulers are plotted as a set of lines with the same origin, forming a hub and spokes. Different parts of the rulers are coloured differently to reflect the frequency (red for a low frequency, blue for a high frequency) with which the corresponding values are observed in a reference set of structures determined previously. The points for a given model marked on these lines are connected to form a polygon. A polygon that is strongly compressed or dilated along some axes reveals unusually low or high values of the corresponding characteristics. Polygon vertices in `red zones' indicate parameters which lie outside typical values. [source] Atomic Interactions and Profile of Small Molecules Disrupting Protein,Protein Interfaces: the TIMBAL DatabaseCHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2009Alícia P. Higueruelo Growing evidence of the possibility of modulating protein,protein interactions with small molecules is opening the door to new approaches and concepts in drug discovery. In this paper, we describe the creation of TIMBAL, a hand-curated database holding an up to date collection of small molecules inhibiting multi-protein complexes. This database has been analysed and profiled in terms of molecular properties. Protein,protein modulators tend to be large lipophilic molecules with few hydrogen bond features. An analysis of TIMBAL's intersection with other structural databases, including CREDO (protein,small molecule from the PDB) and PICCOLO (protein,protein from the PDB) reveals that TIMBAL molecules tend to form mainly hydrophobic interactions with only a few hydrogen bonding contacts. With respect to potency, TIMBAL molecules are slightly less efficient than an average medicinal chemistry hit or lead. The database provides a resource that will allow further insights into the types of molecules favoured by protein interfaces and provide a background to continuing work in this area. Access at http://www-cryst.bioc.cam.ac.uk/timbal [source] | ||||||||||