Dataset Information

Theoretical study of the Usutu virus helicase 3D structure, by means of computer-aided homology modelling.

ABSTRACT:

Background

Usutu virus belongs to the Flaviviridae viral family and constitutes an important pathogen. The viral helicase is an ideal target for inhibitor design, since this enzyme is essential for the survival, proliferation and transmission of the virus.

Results

Towards a drug-design approach, the 3D model of the Usutu virus helicase structure has been designed, using conventional homology modelling techniques and the known 3D-structure of the Murray Valley Encephalitis virus helicase, of the same viral family, as template. The model was then subjected to extended molecular dynamics simulations in a periodic box, filled with explicit water molecules for 10 nanoseconds. The reliability of the model was confirmed by obtaining acceptable scores from a variety of in silico scoring tools, including Procheck and Verify3D.

Conclusion

[corrected] The 3D model of the Usutu virus helicase exhibits in silico all known structural characteristics of the Flaviviridae viral family helicase enzymes and could provide the platform for further de novo structure-based design of novel anti-Usutu agents.

SUBMITTER: Vlachakis D

PROVIDER: S-EPMC2707372 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Theoretical study of the Usutu virus helicase 3D structure, by means of computer-aided homology modelling.

Vlachakis Dimitrios D

Theoretical biology & medical modelling 20090625

<h4>Background</h4>Usutu virus belongs to the Flaviviridae viral family and constitutes an important pathogen. The viral helicase is an ideal target for inhibitor design, since this enzyme is essential for the survival, proliferation and transmission of the virus.<h4>Results</h4>Towards a drug-design approach, the 3D model of the Usutu virus helicase structure has been designed, using conventional homology modelling techniques and the known 3D-structure of the Murray Valley Encephalitis virus he ...[more]

PMID: 19555498

Similar Datasets

Project description:To design a computer-aided detection (CADe) system for clustered microcalcifications in reconstructed digital breast tomosynthesis (DBT) volumes and to perform a preliminary evaluation of the CADe system.IRB approval and informed consent were obtained in this study. A data set of two-view DBT of 72 breasts containing microcalcification clusters was collected from 72 subjects who were scheduled to undergo breast biopsy. Based on tissue sampling results, 17 cases had breast cancer and 55 were benign. A separate data set of two-view DBT of 38 breasts free of clustered microcalcifications from 38 subjects was collected to independently estimate the number of false-positives (FPs) generated by the CADe system. A radiologist experienced in breast imaging marked the biopsied cluster of microcalcifications with a 3D bounding box using all available clinical and imaging information. A CADe system was designed to detect microcalcification clusters in the reconstructed volume. The system consisted of prescreening, clustering, and false-positive reduction stages. In the prescreening stage, the conspicuity of microcalcification-like objects was increased by an enhancement-modulated 3D calcification response function. An iterative thresholding and 3D object growing method was used to detect cluster seed objects, which were used as potential centers of microcalcification clusters. In the cluster detection stage, microcalcification candidates were identified using a second iterative thresholding procedure, which was applied to the signal-to-noise ratio (SNR) enhanced image voxels with a positive calcification response. Starting with each cluster seed object as the initial cluster center, a dynamic clustering algorithm formed a cluster candidate by including microcalcification candidates within a 3D neighborhood of the cluster seed object that satisfied the clustering criteria. The number, size, and SNR of the microcalcifications in a cluster candidate and the cluster shape were used to reduce the number of FPs.The prescreening stage detected a cluster seed object in 94% of the biopsied microcalcification clusters at a threshold of 100 cluster seed objects per DBT volume. After clustering, the detection sensitivity was 90% at 15 marks per DBT volume. After FP reduction, at 85% sensitivity, the average number of FPs estimated using the data set containing microcalcification clusters was 3.8 per DBT volume, and that estimated using the data set free of microcalcification clusters was 3.4. The detection performance for malignant microcalcification clusters was superior to that for benign clusters.Our study indicates the feasibility of the 3D approach to the detection of clustered microcalcifications in DBT and that the newly designed enhancement-modulated 3D calcification response function is promising for prescreening. Further work is needed to assess the generalizability of our approach and to improve its performance.

Project description:BackgroundThe structure of the valve leaflets and sinuses are crucial in supporting the proper function of the semilunar valve and ensuring leaflet durability. Therefore, an enhanced understanding of the structural characteristics of the semilunar valves is fundamental to the evaluation and staging of semilunar valve pathology, as well as the development of prosthetic or bioprosthetic valves. This paper illustrates the process of combining computer-aided design (CAD), 3D printing and flow assessment with 4-dimensional flow magnetic resonance imaging (MRI) to provide detailed assessment of the structural and hemodynamic characteristics of the normal semilunar valve.MethodsPreviously published geometric data on the aortic valve was used to model the 'normal' tricuspid aortic valve with a CAD software package and 3D printed. An MRI compatible flow pump with the capacity to mimic physiological flows was connected to the phantom. A peak flow rate of 100 mL/s and heart rate of 60 beats per minute were used. MRI measurements included cine imaging, 2D and 4D phase-contrast imaging to assess valve motion, flow velocity and complex flow patterns.ResultsCine MRI data showed normal valve function and competency throughout the cardiac cycle in the 3D-printed phantom. Quantitative analysis of 4D Flow data showed net flow through 2D planes proximal and distal to the valve were very consistent (26.03 mL/s and 26.09 mL/s, respectively). Measurements of net flow value agreed closely with the flow waveform provided to the pump (27.74 mL/s), confirming 4D flow acquisition in relation to the pump output. Peak flow values proximal and distal to the valve were 78.4 mL/s and 63.3 mL/s, respectively. Particle traces of flow from 4D-phase contrast MRI data demonstrated flow through the valve into the ascending aorta and vortices within the aortic sinuses, which are expected during ventricular diastole.ConclusionIn this proof of concept study, we have demonstrated the ability to generate physiological 3D-printed aortic valve phantoms and evaluate their function with cine- and 4D Flow MRI. This technology can work synergistically with promising tissue engineering research to develop optimal aortic valve replacements, which closely reproduces the complex function of the normal aortic valve.

Project description:Body mass reconstructions of extinct vertebrates are most robust when complete to near-complete skeletons allow the reconstruction of either physical or digital models. Digital models are most efficient in terms of time and cost, and provide the facility to infinitely modify model properties non-destructively, such that sensitivity analyses can be conducted to quantify the effect of the many unknown parameters involved in reconstructions of extinct animals. In this study we use laser scanning (LiDAR) and computer modelling methods to create a range of 3D mass models of five specimens of non-avian dinosaur; two near-complete specimens of Tyrannosaurus rex, the most complete specimens of Acrocanthosaurus atokensis and Strutiomimum sedens, and a near-complete skeleton of a sub-adult Edmontosaurus annectens. LiDAR scanning allows a full mounted skeleton to be imaged resulting in a detailed 3D model in which each bone retains its spatial position and articulation. This provides a high resolution skeletal framework around which the body cavity and internal organs such as lungs and air sacs can be reconstructed. This has allowed calculation of body segment masses, centres of mass and moments or inertia for each animal. However, any soft tissue reconstruction of an extinct taxon inevitably represents a best estimate model with an unknown level of accuracy. We have therefore conducted an extensive sensitivity analysis in which the volumes of body segments and respiratory organs were varied in an attempt to constrain the likely maximum plausible range of mass parameters for each animal. Our results provide wide ranges in actual mass and inertial values, emphasizing the high level of uncertainty inevitable in such reconstructions. However, our sensitivity analysis consistently places the centre of mass well below and in front of hip joint in each animal, regardless of the chosen combination of body and respiratory structure volumes. These results emphasize that future biomechanical assessments of extinct taxa should be preceded by a detailed investigation of the plausible range of mass properties, in which sensitivity analyses are used to identify a suite of possible values to be tested as inputs in analytical models.

Dataset Information

Theoretical study of the Usutu virus helicase 3D structure, by means of computer-aided homology modelling.

Background

Results

Conclusion

Publications

Theoretical study of the Usutu virus helicase 3D structure, by means of computer-aided homology modelling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets