PONDEROSA-C/S: client–server based software package for automated protein 3D structure determination

Peak-picking Of Noe Data Enabled by Restriction Of Shift Assignments-Client Server (PONDEROSA-C/S) builds on the original PONDEROSA software (Lee et al. in Bioinformatics 27:1727–1728. doi:10.1093/bioinformatics/btr200, 2011) and includes improved features for structure calculation and refinement. PONDEROSA-C/S consists of three programs: Ponderosa Server, Ponderosa Client, and Ponderosa Analyzer. PONDEROSA-C/S takes as input the protein sequence, a list of assigned chemical shifts, and nuclear Overhauser data sets (¹³C- and/or ¹⁵N-NOESY). The output is a set of assigned NOEs and 3D structural models for the protein. Ponderosa Analyzer supports the visualization, validation, and refinement of the results from Ponderosa Server. These tools enable semi-automated NMR-based structure determination of proteins in a rapid and robust fashion. We present examples showing the use of PONDEROSA-C/S in solving structures of four proteins: two that enable comparison with the original PONDEROSA package, and two from the Critical Assessment of automated Structure Determination by NMR (Rosato et al. in Nat Methods 6:625–626. doi:10.1038/nmeth0909-625, 2009) competition. The software package can be downloaded freely in binary format from http://pine.nmrfam.wisc.edu/download_packages.html. Registered users of the National Magnetic Resonance Facility at Madison can submit jobs to the PONDEROSA-C/S server at http://ponderosa.nmrfam.wisc.edu, where instructions, tutorials, and instructions can be found. Structures are normally returned within 1–2 days.     

E-MSD: the European Bioinformatics Institute Macromolecular Structure Database

The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.     

BEID: Database for sequence-structure-function information on antigen-antibody interactions

The B-cell Epitope Interaction Database (BEID; http://datam.i2r.a-star.edu.sg/BEID) is an open-access database describing sequence-structure-function information on immunoglobulin (Ig)-antigen interactions. The current version of the database contains 164 antigens, 126 Ig and 189 Ig-antigen complexes extracted from the Protein Data Bank (PDB). Each entry is manually verified, classified, and analyzed for intermolecular interactions between antigens and the corresponding bound Ig molecules. Ig-antigen interaction information that is stored in BEID includes solvent accessibility, hydrogen bonds, non-hydrogen bonds, gap volume, gap index, interface area and contact residues. The database can be searched with a user-friendly search tool and schematic diagrams for Ig-antigen interactions are available for download in PDF format. The ultimate purpose of BEID is to enhance the understanding of the rules of engagement between antigen and the corresponding bound Ig molecules. It is also a precious data source for developing computational predictors for B-cell epitopes.     

The DynDom database of protein domain motions

A relational database has been developed based on the results from the application of the DynDom program to a number of proteins for which multiple X-ray conformers are available. The database is populated via a web-based tool that allows visitors to the website to run the DynDom program server-side by selecting pairs of X-ray conformers by Protein Data Bank code and chain identifier. AVAILABILITY: The website can be found at: http://www.sys.uea.ac.uk/dyndom.     

Probabilistic Interaction Network of Evidence Algorithm and its Application to Complete Labeling of Peak Lists from Protein NMR Spectroscopy

The process of assigning a finite set of tags or labels to a collection of observations, subject to side conditions, is notable for its computational complexity. This labeling paradigm is of theoretical and practical relevance to a wide range of biological applications, including the analysis of data from DNA microarrays, metabolomics experiments, and biomolecular nuclear magnetic resonance (NMR) spectroscopy. We present a novel algorithm, called Probabilistic Interaction Network of Evidence (PINE), that achieves robust, unsupervised probabilistic labeling of data. The computational core of PINE uses estimates of evidence derived from empirical distributions of previously observed data, along with consistency measures, to drive a fictitious system M with Hamiltonian H to a quasi-stationary state that produces probabilistic label assignments for relevant subsets of the data. We demonstrate the successful application of PINE to a key task in protein NMR spectroscopy: that of converting peak lists extracted from various NMR experiments into assignments associated with probabilities for their correctness. This application, called PINE-NMR, is available from a freely accessible computer server (http://pine.nmrfam.wisc.edu). The PINE-NMR server accepts as input the sequence of the protein plus user-specified combinations of data corresponding to an extensive list of NMR experiments; it provides as output a probabilistic assignment of NMR signals (chemical shifts) to sequence-specific backbone and aliphatic side chain atoms plus a probabilistic determination of the protein secondary structure. PINE-NMR can accommodate prior information about assignments or stable isotope labeling schemes. As part of the analysis, PINE-NMR identifies, verifies, and rectifies problems related to chemical shift referencing or erroneous input data. PINE-NMR achieves robust and consistent results that have been shown to be effective in subsequent steps of NMR structure determination.     

Novel structural tree of (α + β)-proteins containing abCd units

A database of 926 (α + β)-proteins and (α + β)-domains containing abCd units, including 401 non-homologous, was compiled from the Protein Data Bank (total of 2636 PDB entries). A novel structural tree of this structural class of proteins was constructed to include 286 possible polypeptide chain folds. A structural classification of (α + β)-proteins containing abCd unit was developed on the basis of the structural tree. The database and the structural tree are available at http://strees.protres.ru/.     

SALMONELLABASE - An online database of druggable targets of Salmonella species

Salmonellosis is one of the most common and widely distributed food borne diseases caused by Salmonella serovars. The emergence of multi drug resistant strains has become a threatening public health problem and targeting unique effectors of this pathogen can be considered as a powerful strategy for drug design. SalmonellaBase is an online web portal serving as an integrated source of information about Salmonella serovars with the data required for the structural and functional studies and the analysis of druggable targets in Salmonella. We have identified several target proteins, which helps in the pathogenicity of the organism and predicted their structures. The database will have the information on completely sequenced genomes of Salmonella species with the complete set of protein sequences of the respective strains, determined structures, predicted protein structures and biochemical pathways of the respective strains. In addition, we have provided information about name and source of the protein, Uniprot and Protein Data Bank codes and literature information. Furthermore, SalmonellaBase is linked to related databases and other resources. We have set up a web interface with different search and display options so that users have the ability to get the data in several ways. SalmonellaBase is a freely available database.

Availability

http://www.salmonellabase.com/     

CPAD,Curated Protein Aggregation Database: A Repository of Manually Curated Experimental Data on Protein and Peptide Aggregation

Accurate distinction between peptide sequences that can form amyloid-fibrils or amorphous β-aggregates, identification of potential aggregation prone regions in proteins, and prediction of change in aggregation rate of a protein upon mutation(s) are critical to research on protein misfolding diseases, such as Alzheimer’s and Parkinson’s, as well as biotechnological production of protein based therapeutics. We have developed a Curated Protein Aggregation Database (CPAD), which has collected results from experimental studies performed by scientific community aimed at understanding protein/peptide aggregation. CPAD contains more than 2300 experimentally observed aggregation rates upon mutations in known amyloidogenic proteins. Each entry includes numerical values for the following parameters: change in rate of aggregation as measured by fluorescence intensity or turbidity, name and source of the protein, Uniprot and Protein Data Bank codes, single point as well as multiple mutations, and literature citation. The data in CPAD has been supplemented with five different types of additional information: (i) Amyloid fibril forming hexa-peptides, (ii) Amorphous β-aggregating hexa-peptides, (iii) Amyloid fibril forming peptides of different lengths, (iv) Amyloid fibril forming hexa-peptides whose crystal structures are available in the Protein Data Bank (PDB) and (v) Experimentally validated aggregation prone regions found in amyloidogenic proteins. Furthermore, CPAD is linked to other related databases and resources, such as Uniprot, Protein Data Bank, PUBMED, GAP, TANGO, WALTZ etc. We have set up a web interface with different search and display options so that users have the ability to get the data in multiple ways. CPAD is freely available at http://www.iitm.ac.in/bioinfo/CPAD/. The potential applications of CPAD have also been discussed.     

Saccharomyces Genome Database (SGD) provides biochemical and structural information for budding yeast proteins

The Saccharomyces Genome Database (SGD: http://genome-www.stanford.edu/Saccharomyces/) has recently developed new resources to provide more complete information about proteins from the budding yeast Saccharomyces cerevisiae. The PDB Homologs page provides structural information from the Protein Data Bank (PDB) about yeast proteins and/or their homologs. SGD has also created a resource that utilizes the eMOTIF database for motif information about a given protein. A third new resource is the Protein Information page, which contains protein physical and chemical properties, such as molecular weight and hydropathicity scores, predicted from the translated ORF sequence.     

PSST-2.0

PSST-2.0 (Protein Data Bank [PDB] Sequence Search Tool) is an updated version of the earlier PSST (Protein Sequence Search Tool), and the philosophy behind the search engine has remained unchanged. PSST-2.0 is a Web-based, interactive search engine developed to retrieve required protein or nucleic acid sequence information and some of its related details, primarily from sequences derived from the structures deposited in the PDB (the database of 3-dimensional [3-D] protein and nucleic acid structures). Additionally, the search engine works for a selected subset of 25% or 90% non-homologous protein chains. For some of the selected options, the search engine produces a detailed output for the user-uploaded, 3-D atomic coordinates of the protein structure (PDB file format) from the client machine through the Web browser. The search engine works on a locally maintained PDB, which is updated every week from the parent server at the Research Collaboratory for Structural Bioinformatics, and hence the search results are up to date at any given time. AVAILABILITY: PSST-2.0 is freely accessible via http://pranag.physics.iisc.ernet.in/psst/ or http://144.16.71.10/psst/.     

AraPPISite: a database of fine-grained protein–protein interaction site annotations for Arabidopsis thaliana

Knowledge about protein interaction sites provides detailed information of protein–protein interactions (PPIs). To date, nearly 20,000 of PPIs from Arabidopsis thaliana have been identified. Nevertheless, the interaction site information has been largely missed by previously published PPI databases. Here, AraPPISite, a database that presents fine-grained interaction details for A. thaliana PPIs is established. First, the experimentally determined 3D structures of 27 A. thaliana PPIs are collected from the Protein Data Bank database and the predicted 3D structures of 3023 A. thaliana PPIs are modeled by using two well-established template-based docking methods. For each experimental/predicted complex structure, AraPPISite not only provides an interactive user interface for browsing interaction sites, but also lists detailed evolutionary and physicochemical properties of these sites. Second, AraPPISite assigns domain–domain interactions or domain–motif interactions to 4286 PPIs whose 3D structures cannot be modeled. In this case, users can easily query protein interaction regions at the sequence level. AraPPISite is a free and user-friendly database, which does not require user registration or any configuration on local machines. We anticipate AraPPISite can serve as a helpful database resource for the users with less experience in structural biology or protein bioinformatics to probe the details of PPIs, and thus accelerate the studies of plant genetics and functional genomics. AraPPISite is available at http://systbio.cau.edu.cn/arappisite/index.html.     

PSIbase: a database of Protein Structural Interactome map (PSIMAP)

Protein Structural Interactome map (PSIMAP) is a global interaction map that describes domain-domain and protein-protein interaction information for known Protein Data Bank structures. It calculates the Euclidean distance to determine interactions between possible pairs of structural domains in proteins. PSIbase is a database and file server for protein structural interaction information calculated by the PSIMAP algorithm. PSIbase also provides an easy-to-use protein domain assignment module, interaction navigation and visual tools. Users can retrieve possible interaction partners of their proteins of interests if a significant homology assignment is made with their query sequences. AVAILABILITY: http://psimap.org and http://psibase.kaist.ac.kr/     

Enlarged FAMSBASE: protein 3D structure models of genome sequences for 41 species

Enlarged FAMSBASE is a relational database of comparative protein structure models for the whole genome of 41 species, presented in the GTOP database. The models are calculated by Full Automatic Modeling System (FAMS). Enlarged FAMSBASE provides a wide range of query keys, such as name of ORF (open reading frame), ORF keywords, Protein Data Bank (PDB) ID, PDB heterogen atoms and sequence similarity. Heterogen atoms in PDB include cofactors, ligands and other factors that interact with proteins, and are a good starting point for analyzing interactions between proteins and other molecules. The data may also work as a template for drug design. The present number of ORFs with protein 3D models in FAMSBASE is 183 805, and the database includes an average of three models for each ORF. FAMSBASE is available at http://famsbase.bio.nagoya-u.ac.jp/famsbase/.     

BioMagResBank database with sets of experimental NMR constraints corresponding to the structures of over 1400 biomolecules deposited in the Protein Data Bank

Experimental constraints associated with NMR structures are available from the Protein Data Bank (PDB) in the form of `Magnetic Resonance' (MR) files. These files contain multiple types of data concatenated without boundary markers and are difficult to use for further research. Reported here are the results of a project initiated to annotate, archive, and disseminate these data to the research community from a searchable resource in a uniform format. The MR files from a set of 1410 NMR structures were analyzed and their original constituent data blocks annotated as to data type using a semi-automated protocol. A new software program called Wattos was then used to parse and archive the data in a relational database. From the total number of MR file blocks annotated as constraints, it proved possible to parse 84% (3337/3975). The constraint lists that were parsed correspond to three data types (2511 distance, 788 dihedral angle, and 38 residual dipolar couplings lists) from the three most popular software packages used in NMR structure determination: XPLOR/CNS (2520 lists), DISCOVER (412 lists), and DYANA/DIANA (405 lists). These constraints were then mapped to a developmental version of the BioMagResBank (BMRB) data model. A total of 31 data types originating from 16 programs have been classified, with the NOE distance constraint being the most commonly observed. The results serve as a model for the development of standards for NMR constraint deposition in computer-readable form. The constraints are updated regularly and are available from the BMRB web site (http://www.bmrb.wisc.edu).     

TargetDB: a target registration database for structural genomics projects

TargetDB is a centralized target registration database that includes protein target data from the NIH structural genomics centers and a number of international sites. TargetDB, which is hosted by the Protein Data Bank (RCSB PDB), provides status information on target sequences and tracks their progress through the various stages of protein production and structure determination. A simple search form permits queries based on contributing site, target ID, protein name, sequence, status and other data. The progress of individual targets or entire structural genomics projects may be tracked over time, and target data from all contributing centers may also be downloaded in the XML format. AVAILABILITY: TargetDB is available at http://targetdb.pdb.org/     

ProTherm: Thermodynamic Database for Proteins and Mutants.

The first release of the Thermodynamic Database for Proteins and Mutants (ProTherm) contains more than 3300 data of several thermodynamic parameters for wild type and mutant proteins. Each entry includes numerical data for unfolding Gibbs free energy change, enthalpy change, heat capacity change, transition temperature, activity etc., which are important for understanding the mechanism of protein stability. ProTherm also includes structural information such as secondary structure and solvent accessibility of wild type residues, and experimental methods and other conditions. A WWW interface enables users to search data based on various conditions with different sorting options for outputs. Further, ProTherm is cross-linked with NCBI PUBMED literature database, Protein Mutant Database, Enzyme Code and Protein Data Bank structural database. Moreover, all the mutation sites associated with each PDB structure are automatically mapped and can be directly viewed through 3DinSight developed in our laboratory. The database is available at the URL, http://www.rtc.riken.go.jp/protherm.htm l     

Beta-lactamase database (BLDB) – structure and function

Beta-Lactamase Database (BLDB) is a comprehensive, manually curated public resource providing up-to-date structural and functional information focused on this superfamily of enzymes with a great impact on antibiotic resistance. All the enzymes reported and characterised in the literature are presented according to the class (A, B, C and D), family and subfamily to which they belong. All three-dimensional structures of β-lactamases present in the Protein Data Bank are also shown. The characterisation of representative mutants and hydrolytic profiles (kinetics) completes the picture and altogether these four elements constitute the essential foundation for a better understanding of the structure-function relationship within this enzymes family. BLDB can be queried using different protein- and nucleotide-based BLAST searches, which represents a key feature of particular importance in the context of the surveillance of the evolution of the antibiotic resistance. BLDB is available online at http://bldb.eu without any registration and supports all modern browsers.     

The HSSP database of protein structure-sequence alignments and family profiles.

HSSP (http: //www.sander.embl-ebi.ac.uk/hssp/) is a derived database merging structure (3-D) and sequence (1-D) information. For each protein of known 3D structure from the Protein Data Bank (PDB), we provide a multiple sequence alignment of putative homologues and a sequence profile characteristic of the protein family, centered on the known structure. The list of homologues is the result of an iterative database search in SWISS-PROT using a position-weighted dynamic programming method for sequence profile alignment (MaxHom). The database is updated frequently. The listed putative homologues are very likely to have the same 3D structure as the PDB protein to which they have been aligned. As a result, the database not only provides aligned sequence families, but also implies secondary and tertiary structures covering 33% of all sequences in SWISS-PROT.