| 1. |
- Boulund, Fredrik, 1985, et al.
(författare)
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An analytical solution for finding voids and bottlenecks within macromolecules
- 2009
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Ingår i: 3DSig 2009: The 5th Structural Bioinformatics and Computational Biophysics Meeting, Stockholm, Sweden, 27-28 June 2009. ; , s. 77-78
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We present an implementation of a direct analytical method for finding the largest sphere inscribed by four others. This method has been applied to the identification of voids and bottlenecks in protein channels.
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| 2. |
- Chalmers, Stuart, 1973, et al.
(författare)
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An Ontology-Based Approach to Car Simulation and Design
- 2008
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Ingår i: Third Asian Semantic Web Conference, ASWC2008 Bangkok, Thailand December 2008, Workshops Proceedings. ; , s. 270-275
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Konferensbidrag (refereegranskat)abstract
- The complex functionality of modern road vehicles is to a large extent controlled by computer hardware and software. One way to manage this complexity is to test models, hardware and driver behaviour by simulating them in early phases of system development, using driving simulators and data communication systems to test both physical and virtual components and their interactions within existing systems. This requires well-defined interfaces and configurable, general methods for communication between components using disparate protocols. In this paper we describe an ontology-based approach to provide a commonvocabulary for simulation and component interaction and testing in the early design phase of vehicle control system development. The benefits that an ontology-based approach brings to this application are discussed.
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| 3. |
- Cvijovic, Marija, 1977, et al.
(författare)
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Identification of putative regulatory upstream ORFs in the yeast genome using heuristics and evolutionary conservation
- 2007
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The translational efficiency of an mRNA can be modulated by upstream open reading frames (uORFs) present in certain genes. A uORF can attenuate translation of the main ORF by interfering with translational reinitiation at the main start codon. uORFs also occur by chance in the genome, in which case they do not have a regulatory role. Since the sequence determinants for functional uORFs are not understood, it is difficult to discriminate functional from spurious uORFs by sequence analysis. RESULTS: We have used comparative genomics to identify novel uORFs in yeast with a high likelihood of having a translational regulatory role. We examined uORFs, previously shown to play a role in regulation of translation in Saccharomyces cerevisiae, for evolutionary conservation within seven Saccharomyces species. Inspection of the set of conserved uORFs yielded the following three characteristics useful for discrimination of functional from spurious uORFs: a length between 4 and 6 codons, a distance from the start of the main ORF between 50 and 150 nucleotides, and finally a lack of overlap with, and clear separation from, neighbouring uORFs. These derived rules are inherently associated with uORFs with properties similar to the GCN4 locus, and may not detect most uORFs of other types. uORFs with high scores based on these rules showed a much higher evolutionary conservation than randomly selected uORFs. In a genome-wide scan in S. cerevisiae, we found 34 conserved uORFs from 32 genes that we predict to be functional; subsequent analysis showed the majority of these to be located within transcripts. A total of 252 genes were found containing conserved uORFs with properties indicative of a functional role; all but 7 are novel. Functional content analysis of this set identified an overrepresentation of genes involved in transcriptional control and development. CONCLUSION: Evolutionary conservation of uORFs in yeasts can be traced up to 100 million years of separation. The conserved uORFs have certain characteristics with respect to length, distance from each other and from the main start codon, and folding energy of the sequence. These newly found characteristics can be used to facilitate detection of other conserved uORFs.
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| 4. |
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| 5. |
- Fernandez-Ricaud, Luciano, 1975, et al.
(författare)
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PROPHECY - a database for high-resolution phenomics
- 2005
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- The rapid recent evolution of the field phenomics—the genome-wide study of gene dispensability by quantitative analysis of phenotypes—has resulted in an increasing demand for new data analysis and visualization tools. Following the introduction of a novel approach for precise, genome-wide quantification of gene dispensability in Saccharomyces cerevisiae we here announce a public resource for mining, filtering and visualizing phenotypic data—the PROPHECY database. PROPHECY is designed to allow easy and flexible access to physiologically relevant quantitative data for the growth behaviour of mutant strains in the yeast deletion collection during conditions of environmental challenges. PROPHECY is publicly accessible at http://prophecy.lundberg.gu.se.
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| 6. |
- Fernandez-Ricaud, Luciano, 1975, et al.
(författare)
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PROPHECY—a yeast phenome database, update 2006
- 2007
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Connecting genotype to phenotype is fundamental in biomedical research and in our understanding of disease. Phenomics—the large-scale quantitative phenotypic analysis of genotypes on a genome-wide scale—connects automated data generation with the development of novel tools for phenotype data integration, mining and visualization. Our yeast phenomics database PROPHECY is available at http://prophecy.lundberg.gu.se. Via phenotyping of 984 heterozygous diploids for all essential genes the genotypes analysed and presented in PROPHECY have been extended and now include all genes in the yeast genome. Further, phenotypic data from gene overexpression of 574 membrane spanning proteins has recently been included. To facilitate the interpretation of quantitative phenotypic data we have developed a new phenotype display option, the Comparative Growth Curve Display, where growth curve differences for a large number of mutants compared with the wild type are easily revealed. In addition, PROPHECY now offers a more informative and intuitive first-sight display of its phenotypic data via its new summary page. We have also extended the arsenal of data analysis tools to include dynamic visualization of phenotypes along individual chromosomes. PROPHECY is an initiative to enhance the growing field of phenome bioinformatics
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| 7. |
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| 8. |
- Gray, P. M. D., et al.
(författare)
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Capturing Quantified Constraints in FOL, Through Interaction with a Relationship Graph
- 2006
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Ingår i: Managing Knowledge in a World of Networks: 15th International Conference, EKAW 2006, Lecture Notes in Computer Science. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783540463634 ; 4248, s. 19-26
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Konferensbidrag (refereegranskat)abstract
- As new semantic web standards evolve to allow quantified rules in FOL, we need new ways to capture them from end users in RDFS(XML). We show how to do this against a graphic view of Entities and their Relationships (associated or derived). This even allows inclusion of existential quantifiers in readable fashion. The captured constraint can be tested by generating queries to search for violations in stored data. The constraint can then be automatically revised to exclude specific cases picked out by the user, who is spared worries about proper syntax and boolean connectives.
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| 9. |
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| 10. |
- Kemp, Graham, 1965, et al.
(författare)
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Architecture of a mediator for a bioinformatics database federation
- 2002
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Ingår i: IEEE Transactions on Information Technology in Biomedicine. - 1089-7771. ; 6:2, s. 116-122
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Tidskriftsartikel (refereegranskat)abstract
- Developments in our ability to integrate and analyze data held in existing heterogeneous data resources can lead to an increase in our understanding of biological function at all levels. However, supporting ad hoc queries across multiple data resources and correlating data retrieved from these is still difficult. To address this, we are building a mediator based on the functional data model database, P/FDM, which integrates access to heterogeneous distributed biological databases. Our architecture makes use of the existing search capabilities and indexes of the underlying databases, without infringing on their autonomy. Central to our design philosophy is the use of schemas. We have adopted a federated architecture with a five-level schema, arising from the use of the ANSI-SPARC three-level schema to describe both the existing autonomous data resources and the mediator itself. We describe the use of mapping functions and list comprehensions in query splitting, producing execution plans, code generation, and result fusion. We give an example of cross-database querying involving data held locally in P/FDM systems and external data in SRS.
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| 11. |
- Kemp, Graham, 1965, et al.
(författare)
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Modelling Biological Data in Hierarchies
- 2002
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Ingår i: 10th International Conference on Intelligent Systems for Molecular Biology, Edmonton, Canada, 3-7 August 2002.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Kemp, Graham, 1965
(författare)
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Models of Database Interconnectivity
- 2005
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Ingår i: Database Annotation in Molecular Biology: Principles and Practice. - 0470856815 ; , s. 203-221
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 13. |
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| 14. |
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| 15. |
- Kemp, Graham, 1965, et al.
(författare)
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Pathway and Protein Interaction Data: from XML to FDM Database
- 2004
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Ingår i: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1611-3349 .- 0302-9743. - 3540213007 ; 2994, s. 212-219
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes our experience with the first steps towards integrating pathway and protein interaction data with other data sets within the framework of a federated database system based on the functional data model. We have made use of DTD and XML files produced by the BIND project. The DTD provides a specification for information about biomolecular interactions, complexes and pathways, and can be translated semi-automatically to a database schema. The load utility uses metadata derived from this schema to help identify data items of interest when recursively traversing a Prolog tree structure representing the XML data. We also show how derived functions can be used to make explicit those relationships that are present in data sets but which are not fully described in DTD files.
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| 16. |
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| 17. |
- Koppisetty, Ashok Krishna Chaitanya, 1982, et al.
(författare)
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Computation of Binding Energies Including Their Enthalpy and Entropy Components for Protein-Ligand Complexes Using Support Vector Machines
- 2013
-
Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X .- 0095-2338 .- 1520-5142. ; 53:10, s. 2559-2570
-
Tidskriftsartikel (refereegranskat)abstract
- Computing binding energies of protein-ligand complexes including their enthalpy and entropy terms by means of computational methods is an appealing approach for selecting initial hits and for further optimization in early stages of drug discovery. Despite the importance, computational predictions of thermodynamic components have evaded attention and reasonable solutions. In this study, support vector machines are used for developing scoring functions to compute binding energies and their enthalpy and entropy components of protein-ligand complexes. The binding energies computed from our newly derived scoring functions have better Pearson's correlation coefficients with experimental data than previously reported scoring functions in benchmarks for protein-ligand complexes from the PDBBind database. The protein-ligand complexes with binding energies dominated by enthalpy or entropy term could be qualitatively classified by the newly derived scoring functions with high accuracy. Furthermore, it is found that the inclusion of comprehensive descriptors based on ligand properties in the scoring functions improved the accuracy of classification as well as the prediction of binding energies including their thermodynamic components. The prediction of binding energies including the enthalpy and entropy components using the support vector machine based scoring functions should be of value in the drug discovery process.
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| 18. |
- Koussounadis, Antonis I., et al.
(författare)
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Analysis of Fish IL-1beta and Derived Peptide Sequences Indicates Conserved Structures with Species-Specific IL-1 Receptor Binding: Implications for Pharmacological Design
- 2004
-
Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1873-4286 .- 1381-6128. ; 10:31, s. 3857-3871
-
Tidskriftsartikel (refereegranskat)abstract
- A large number of IL-1 protein sequences have become available recently from a range of vertebrate species and especially from bony fish. However, 3D structures are still only known for mammalian IL-1. In this review, we use a multiple sequence alignment of all published non-mammalian vertebrate IL-1beta proteins to locate the structurally important residues critical for maintaining the beta-trefoil fold and we investigate the degree to which functionally important residues involved in receptor binding are conserved across vertebrate species. We find that although there is a high level of variability of positions involved in receptor binding, the mode of binding and overall shape of the ligand-receptor complex is probably maintained. This implies that each species has evolved its own unique interleukin-1 signalling system through ligand-receptor co-evolution. Nonetheless, the IL-1beta processing mechanism in non-mammalian vertebrates remains unclear because, with the exception of three bony fish, all non-mammalian IL-1beta sequences discovered so far lack an ICE (Interleukin Converting Enzyme) cut site. The IL-1 system has become an important drug target because of its significance in inflammatory diseases. Research on peptides derived from IL-1beta has identified peptides that possess agonist activity in humans and in trout, and peptides with antagonist activity. The agonist peptides map to two distinct loop regions of IL-1beta that are known to interact with the flexible domain III of the corresponding receptor. Further analysis of the IL-1 system may prove useful in engineering IL-1 with improved features and in suggesting new avenues for therapeutic intervention.
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| 19. |
- Martins, João, et al.
(författare)
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A Functional Data Model Approach to Querying RDF/RDFS Data
- 2008
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Ingår i: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1611-3349 .- 0302-9743. - 9783540705031 ; 5071, s. 153-164
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Konferensbidrag (refereegranskat)abstract
- We are developing a multi-database architecture to provide integrated access to heterogeneous, distributed databases. The work described here is motivated by the desire to have RDF/RDFS collections as component data resources in this system, along with relational and other databases. To achieve this, the RDF/RDFS collection, like all other component resources in the system, is mapped to the functional data model, and a query translator is implemented that can translate queries originally expressed in Daplex (the query language associated with the functional data model) into SPARQL. SPARQL is the prominent query language for RDF and it is used here to bridge between the functional data model and the Semantic Web.
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| 20. |
- Mehio, W., et al.
(författare)
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Identification of protein binding surfaces using surface triplet propensities
- 2010
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 26:20, s. 2549-2555
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: The ability to reliably predict protein-protein and protein-ligand interactions is important for identifying druggable binding sites and for understanding how proteins communicate. Most currently available algorithms identify cavities on the protein surface as potential ligand recognition sites. The method described here does not explicitly look for cavities but uses small surface patches consisting of triplets of adjacent surface atomic groups that can be touched simultaneously by a probe sphere representing a solvent molecule. A total of 455 different types of triplets can be identified. A training set of 309 protein-ligand protein X-ray structures has been used to generate interface propensities for the triplets, which can be used to predict their involvement in ligand-binding interactions. Results: The success rate for locating protein-ligand binding sites on protein surfaces using this new surface triplet propensities (STP) algorithm is 88% which compares well with currently available grid-based and energy-based approaches. Q-SiteFinder's dataset (Laurie and Jackson, 2005. Bioinformatics, 21, 1908-1916) was used to show the favorable performance of STP. An analysis of the different triplet types showed that higher ligand binding propensity is related to more polarizable surfaces. The interaction statistics between triplet atoms on the protein surface and ligand atoms have been used to estimate statistical free energies of interaction. The delta G(stat) for halogen atoms interacting with hydrophobic triplets is -0.6 kcal/mol and an estimate of the maximal delta G(stat) for a ligand atom interacting with a triplet in a binding pocket is -1.45 kcal/mol.
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| 21. |
- Mehio, Wissam, et al.
(författare)
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STP: A Program to Predict Protein Binding Surfaces
- 2009
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Ingår i: 3DSig 2009: The 5th Structural Bioinformatics and Computational Biophysics Meeting, Stockholm, Sweden, 27-28 June 2009. ; , s. 51-52
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We present a novel algorithm, STP (Surface Triangle Profile) to predict protein-ligand binding sites. This algorithm uses the chemical composition of the surface of the protein to assess the likelihood of a certain patch at the surface to be a binding site.
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| 22. |
- Mehio, Wissam, et al.
(författare)
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Using surface patch profiles to predict protein-protein binding surfaces
- 2007
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Ingår i: 3DSig: The 3rd Structural Bioinformatics and Computational Biophysics Meeting, Vienna, Austria, 19-20 July 2007. ; , s. 43-44
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A profile-based method for predicting potential protein-protein binding surfaces is presented. These profiles, derived from the abundance of small surface patches consisting of triplets of adjacent surface atomic groups at protein-protein interfaces and elsewhere, have been used to assess potential binding surfaces and predicted docking orientations with promising initial results.
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| 23. |
- Morris, John A, et al.
(författare)
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An atlas of genetic influences on osteoporosis in humans and mice.
- 2019
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 51, s. 258-266
-
Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR)=58, P=1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P<0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
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| 24. |
- Nyholm, Per-Georg, 1958, et al.
(författare)
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The use of a genetic algorithm search for molecular mechanics (MM3)-based conformational analysis of oligosaccharides.
- 2005
-
Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 340:5, s. 1059-1064
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Tidskriftsartikel (refereegranskat)abstract
- We have implemented a system called glygal that can perform conformational searches on oligosaccharides using several different genetic algorithm (GA) search methods. The searches are performed in the torsion angle conformational space, considering both the primary glycosidic linkages as well as the pendant groups (C-5–C-6 and hydroxyl groups) where energy calculations are performed using the MM3(96) force field. The system includes a graphical user interface for setting calculation parameters and incorporates a 3D molecular viewer. The system was tested using dozens of structures and we present two case studies for two previously investigated O-specific oligosaccharides of the Shigella dysenteriae type 2 and 4. The results obtained using glygal show a significant reduction in the number of structures that need to be sampled in order to find the best conformation, as compared to filtered systematic search.
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| 25. |
- Olsson, Caroline, 1970, et al.
(författare)
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Standardizing radiation oncology data for future modelling of side effects after radiation therapy
- 2011
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Ingår i: 1st International Workshop on Managing Interoperability and compleXity in Health Systems, MIXHS'11, Collocated with the 20th ACM International Conference on Information and Knowledge Management, CIKM 2011 Glasgow 28 October 2011 through 28 October 2011. - New York, NY, USA : ACM. - 9781450309547 ; oct 28, s. 67-70
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Konferensbidrag (refereegranskat)abstract
- Wider acceptance of data standards in radiation oncology would facilitate pooling of data from different studies. In turn, this would help clinicians and medical physicists to better understand the relationships between radiation treatments and consequent late developing side effects, and to design treatment plans that improve patients' quality of life. In this paper, we describe challenges of collecting and integrating radiation oncology data from medical records and treatment planning systems for the purpose of modelling side effects after radiation therapy. © 2011 ACM.
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| 26. |
- Selpi, Selpi, 1977, et al.
(författare)
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A First Step towards Learning which uORFs Regulate Gene Expression
- 2006
-
Ingår i: Journal of integrative bioinformatics. - 1613-4516. ; 3:2, s. 31-
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Tidskriftsartikel (refereegranskat)abstract
- We have taken a first step towards learning which upstream Open Reading Frames (uORFs) regulate gene expression (i.e., which uORFs are functional) in the yeast Saccharomyces cerevisiae. We do this by integrating data from several resources and combining a bioinformatics tool, ORF Finder, with a machine learning technique, inductive logic programming (ILP). Here, we report the challenge of using ILP as part of this integrative system, in order to automatically generate a model that identifies functional uORFs. Our method makes searching for novel functional uORFs more efficient than random sampling. An attempt has been made to predict novel functional uORFs using our method. Some preliminary evidence that our model may be biologically meaningful is presented.
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| 27. |
- Selpi, Selpi, 1977, et al.
(författare)
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Predicting functional upstream open reading frames in Saccharomyces cerevisiae
- 2009
-
Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Some upstream open reading frames (uORFs) regulate gene expression (i.e., they are functional) and can play key roles in keeping organisms healthy. However, how uORFs are involved in gene regulation is not yet fully understood. In order to get a complete view of how uORFs are involved in gene regulation, it is expected that a large number of experimentally verified functional uORFs are needed. Unfortunately, wet-experiments to verify that uORFs are functional are expensive. Results: In this paper, a new computational approach to predicting functional uORFs in the yeast Saccharomyces cerevisiae is presented. Our approach is based on inductive logic programming and makes use of a novel combination of knowledge about biological conservation, Gene Ontology annotations and genes' responses to different conditions. Our method results in a set of simple and informative hypotheses with an estimated sensitivity of 76%. The hypotheses predict 301 further genes to have 398 novel functional uORFs. Three (RPC11, TPK1, and FOL1) of these 301 genes have been hypothesised, following wet-experiments, by a related study to have functional uORFs. A comparison with another related study suggests that eleven of the predicted functional uORFs from genes LDB17, HEM3, CIN8, BCK2, PMC1, FAS1, APP1, ACC1, CKA2, SUR1, and ATH1 are strong candidates for wet-lab experimental studies. Conclusions: Learning based prediction of functional uORFs can be done with a high sensitivity. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help to elucidate the regulatory roles of uORFs.
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| 28. |
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| 29. |
- Selpi, Selpi, 1977, et al.
(författare)
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Using mRNA Secondary Structure Predictions Improves Recognition of Known Yeast Functional uORFs
- 2008
-
Ingår i: Wehenkel, L., d'Alché-Buc, F., Moreau, Y. and Geurts, P. (eds.) MLSB08, The Second International Workshop on Machine Learning in Systems Biology, Brussels, 13-14 September 2008.. ; , s. 85-93
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Konferensbidrag (refereegranskat)abstract
- We are interested in using inductive logic programming (ILP) to generate rules for recognising functional upstream open reading frames (uORFs) in the yeast Saccharomyces cerevisiae. This paper empirically investigates whether providing an ILP system with predicted mRNA secondary structure can increase the performance of the resulting rules. Two sets of experiments, with and without mRNA secondary structure predictions as part of thebackground knowledge, were run. For each set, stratified 10-fold cross-validation experiments were run 100 times, each time randomly permuting the order of the positive training examples, and the performance of the resulting hypotheses were measured. Our results demonstrate that the performance of an ILP system in recognising known functional uORFs in the yeast S. cerevisiae significantly increases when mRNA secondary structure predictions are added to the background knowledge and suggest that mRNA secondary structure can affect the ability of uORFs to regulate gene expression.
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| 30. |
- Strino, Francesco, 1980, et al.
(författare)
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Conformation of the exopolysaccharide of Burkholderia cepacia predicted with molecular mechanics (MM3) using genetic algorithm search.
- 2005
-
Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 340:5, s. 1019-1024
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Tidskriftsartikel (refereegranskat)abstract
- We present a computational conformational analysis of the exopolysaccharide of Burkholderia cepacia, which is believed to play a role in colonization and persistence of B. cepacia in the lungs of cystic fibrosis patients. The repeating unit of the exopolysaccharide is a heptasaccharide with three branches, which cause significant steric restraints. Conformational searches using glygal, an in-house developed software using genetic algorithm search methods, were performed on fragments as well as on the complete repeating unit with wrap-over residues. The force field used for the calculations was MM3(96). The search showed four favored conformations for an isolated repeating unit. However, for a sequence of several repeating units, the calculations indicate a single, well-defined linear conformation.
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| 31. |
- Swain, Martin T., et al.
(författare)
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Predicting peptide interactions with model class II MHC structures
- 2005
-
Ingår i: International Journal on Artificial Intelligence Tools. - 0218-2130. ; 14:4, s. 561-575
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Tidskriftsartikel (refereegranskat)abstract
- An automated method for constructing 3D models of class II MHC structures that uses constraint logic programming to select side-chain conformations is described. This method follows a comparative modeling approach in basing the model structures on experimentally determined MHC-peptide structures, but it uses constraints to ease open the peptide binding groove so that the modeled MHC structure is a less specific fit for the co-crystallized peptide in the starting structure. The resulting models are used by a "peptide threading" program that attempts to predict peptides from a protein sequence that will bind strongly to particular MHC alleles. Our results indicate that MHC models that have been constructed in this way enable the peptide threading program to make binding predictions that are comparable with those obtained when using experimentally determined MHC structures, suggesting that a combined modeling and peptide threading approach is worth pursuing for MHC molecules for which experimentally determined structures are not available.
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| 32. |
- Utriainen, Tapani, 1974, et al.
(författare)
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Using long fragments to reconstruct RNA backbones
- 2007
-
Ingår i: Proceedings of the 7th IEEE International Conference on Bioinformatics and Bioengineering. - 1424415098 ; , s. 1424-1428
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Konferensbidrag (refereegranskat)abstract
- This study addresses to what extent RNA backbones consist of long, recurring fragments. A dynamic programming algorithm is presented that finds the smallest set of fragments that are required to reconstruct the backbone of a known macromolecule within a given root mean square bound. This algorithm is guaranteed to find a global minimum. The program has been used for reconstructing the backbones of several known RNA structures, using fragments taken from ribosomal RNA. Each of these target structures could be approximated within a root mean square deviation of 1.0Å using fragments with an average length of more than eight nucleotides.
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| 33. |
- Wånggren, Maryana, 1988, et al.
(författare)
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Computational protein modelling based on limited sets of constraints
- 2016
-
Ingår i: Proceedings of the 12th International Workshop on Constraint-Based Methods for Bioinformatics. - 9783319449524 ; , s. 99-113
-
Konferensbidrag (refereegranskat)abstract
- Molecular dynamics simulations, often combined with sim-ulated annealing, are commonly used when calculating structural mod-els of proteins, e.g. based on NMR experiments. However, one is oftenfaced with limited and sometimes insufficient information for determin-ing a well-resolved 3D structure. In addition, the type of data availablefor different proteins may vary: ranges for torsion angles, distance ap-proximations, relative orientation of different molecular parts etc. Weare using whatever structural information is around, together with adynamic programming approach for searching the space of feasible con-formations to rapidly determine 3D structures that are consistent withthe input constraints. Time-efficiency is important for good samplingof the conformational space but also to replace expensive, complex andtime consuming experiments. Our approach benefits from having bothhigh level and low level descriptions of conformational features and con-straints, and the possibility to infer new constraints from those that aregiven.
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| 34. |
- Yeturu, Kalidas, et al.
(författare)
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An automated framework for understanding structural variations in the binding grooves of MHC class II molecules
- 2010
-
Ingår i: BMC Bioinformatics. - 1471-2105. ; 11:Suppl 1, s. S55-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: MHC/HLA class II molecules are important components of the immune system and play a critical role in processes such as phagocytosis. Understanding peptide recognition properties of the hundreds of MHC class II alleles is essential to appreciate determinants of antigenicity and ultimately to predict epitopes. While there are several methods for epitope prediction, each differing in their success rates, there are no reports so far in the literature to systematically characterize the binding sites at the structural level and infer recognition profiles from them.RESULTS: Here we report a new approach to compare the binding sites of MHC class II molecules using their three dimensional structures. We use a specifically tuned version of our recent algorithm, PocketMatch. We show that our methodology is useful for classification of MHC class II molecules based on similarities or differences among their binding sites. A new module has been used to define binding sites in MHC molecules. Comparison of binding sites of 103 MHC molecules, both at the whole groove and individual sub-pocket levels has been carried out, and their clustering patterns analyzed. While clusters largely agree with serotypic classification, deviations from it and several new insights are obtained from our study. We also present how differences in sub-pockets of molecules associated with a pair of autoimmune diseases, narcolepsy and rheumatoid arthritis, were captured by PocketMatch13.CONCLUSION: The systematic framework for understanding structural variations in MHC class II molecules enables large scale comparison of binding grooves and sub-pockets, which is likely to have direct implications towards predicting epitopes and understanding peptide binding preferences.
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| 35. |
- Yeturu, Kalidas, et al.
(författare)
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Deriving binding site signatures in MHC Class II molecules, using a novel algorithm
- 2009
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Ingår i: 17th Annual International Conference on Intelligent Systems for Molecular Biology & 8th European Conference on Computational Biology (ISMB/ECCB 2009), Stockholm, Sweden, 27 June to 2 July 2009.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A thorough knowledge of the binding sites of MHC Class II molecules,important components of the immune system, will be of immense help in designing or identifying peptide antigens for rational vaccine design. Here we report a new algorithm to compare structures of binding sites of MHC class II molecules.
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