| 1. |
- Höglund, Pär J., 1980-
(författare)
-
Identification, Characterization and Evolution of Membrane-bound Proteins
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Membrane proteins constitute approximately 30% of all genes in the human genome and two large families of membrane proteins are G protein-coupled receptors (GPCRs) and Solute Carriers (SLCs) with about 800 and 380 human genes, respectively.In Papers I, II and IV, we report 16 novel human Adhesion GPCRs found by searches in NCBI and Celera databases. In Paper I, we report eight novel human GPCRs, and six in Paper II. We identified two new human Adhesion GPCRs and 17 mouse orthologs in Paper IV. Phylogenetic analysis demonstrates that the 16 novel human genes are additional members of the Adhesion GPCR family and can be divided into eight phylogenetic groups. EST expression charts for the entire repertoire of Adhesions in human and mouse were established, showing widespread distribution in both central and peripheral tissues. Different domains were found in their N-terminus, some, such as pentraxin in GPR112, indicates that they take part in immunological processes.In Paper III, we discovered seven new human Rhodopsin GPCRs.In Paper V, we present the identification of two new human genes, termed SLC6A17 and SLC6A18 from the Solute Carriers family 6 (SLC6). We also identified the corresponding orthologs and additional genes from the mouse and rat genomes. We analysed, in total, 430 unique SLC6 proteins from 10 animal, one plant, two fungi and 196 bacterial genomes.In Paper VI, we provide the first systematic analysis of the evolutionary history of the different SLC families in Eukaryotes. In all, we analysed 2403 sequences in eight species and we delineate the evolutionary history of each of the 46 SLC families.
|
|
| 2. |
- Ison, Jon, et al.
(författare)
-
The bio.tools registry of software tools and data resources for the life sciences
- 2019
-
Ingår i: Genome Biology. - : BMC. - 1465-6906 .- 1474-760X. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Bioinformaticians and biologists rely increasingly upon workflows for the flexible utilization of the many life science tools that are needed to optimally convert data into knowledge. We outline a pan-European enterprise to provide a catalogue () of tools and databases that can be used in these workflows. bio.tools not only lists where to find resources, but also provides a wide variety of practical information.
|
|
| 3. |
- Joosten, Robbie P., et al.
(författare)
-
PDB_REDO : automated re-refinement of X-ray structure models in the PDB
- 2009
-
Ingår i: Journal of applied crystallography. - 0021-8898 .- 1600-5767. ; 42, s. 376-384
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 4. |
- Pettifer, Steve, et al.
(författare)
-
The EMBRACE web service collection
- 2010
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 38, s. W683-W688
-
Tidskriftsartikel (refereegranskat)abstract
- The EMBRACE ( European Model for Bioinformatics Research and Community Education) web service collection is the culmination of a 5-year project that set out to investigate issues involved in developing and deploying web services for use in the life sciences. The project concluded that in order for web services to achieve widespread adoption, standards must be defined for the choice of web service technology, for semantically annotating both service function and the data exchanged, and a mechanism for discovering services must be provided. Building on this, the project developed: EDAM, an ontology for describing life science web services; BioXSD, a schema for exchanging data between services; and a centralized registry (http://www.embraceregistry.net) that collects together around 1000 services developed by the consortium partners. This article presents the current status of the collection and its associated recommendations and standards definitions.
|
|
| 5. |
- Read, Randy J., et al.
(författare)
-
A New Generation of Crystallographic Validation Tools for the Protein Data Bank
- 2011
-
Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 19:10, s. 1395-1412
-
Tidskriftsartikel (refereegranskat)abstract
- This report presents the conclusions of the X-ray Validation Task Force of the worldwide Protein Data Bank (PDB). The PDB has expanded massively since current criteria for validation of deposited structures were adopted, allowing a much more sophisticated understanding of all the components of macromolecular crystals. The size of the PDB creates new opportunities to validate structures by comparison with the existing database, and the now-mandatory deposition of structure factors creates new opportunities to validate the underlying diffraction data. These developments highlighted the need for a now assessment of validation criteria. The Task Force recommends that a small set of validation data be presented in an easily understood format, relative to both the full PDB and the applicable resolution class, with greater detail available to interested users. Most importantly, we recommend that referees and editors judging the quality of structural experiments have access to a concise summary of well-established quality indicators.
|
|
| 6. |
- Stary, Anna, et al.
(författare)
-
Toward a Consensus Model of the hERG Potassium Channel
- 2010
-
Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 5:3, s. 455-467
-
Tidskriftsartikel (refereegranskat)abstract
- Malfunction of hERG potassium channels, due to inherited mutations or inhibition by drugs, can cause long QT syndrome, which can lead to life-threatening arrhythmias. A three-dimensional structure of hERG is a prerequisite to understand the molecular basis of hERG malfunction. To achieve a consensus model, we carried out an extensive analysis of hERG models based on various alignments of helix S5. We analyzed seven models using a combination of conventional geometry/packing/normality validation methods as well as molecular dynamics simulations and molecular docking. A synthetic test set with the X-ray crystal structure of K(v)1.2 with artificially shifted S5 sequences modeled into the structure served as a reference case. We docked the known hERG inhibitors (+)-cisapride, (S)-terfenadine, and MK-499 into the hERG models and simulation snapshots. None of the single analyses unambiguously identified a preferred model, but the combination of all three revealed that there is only one model that fulfils all quality criteria. This model is confirmed by a recent mutation scanning experiment (P. Ju, G. Pages, R. R Riek, P. C. Chen, A. M. Torres, R S. Bansal, S. Kuyucak, R W. Kuchel, J. I. Vandenberg, J. Biol. Chem. 2009, 284, 1000-1008).([1]) We expect the modeled structure to be useful as a basis both for computational studies of channel function and kinetics as well as the design of experiments.
|
|
