scholarly journals Modeling and validation of L-asparaginase enzyme, an anticancer agent using the tools of computational biology

2019 ◽  
Vol 8 (1) ◽  
pp. 211
Author(s):  
Praveen Reddy P.
Keyword(s):  
Anticancer Agent ◽  
Structural Model ◽  
Three Dimensional ◽  
Site Directed Mutagenesis ◽  
Subtilis Strain ◽  
Ramachandran Plot ◽  
Enzyme Protein ◽  
Fasta Format ◽  
Microbial Strains ◽  
D Model

Background: The L-Asparaginase is a medically important drug. The L-Asparaginase enzyme, an anticancer agent produced by microorganisms is used for the treatment of patients suffering from lymphoma and leukemia. The L-Asparaginase is economical and its administration is easy when compared to other commercial drugs available in market. Many microbes have been reported to produce the L-Asparaginase.Methods: In the present work the sequence of L-Asparaginase enzyme protein was obtained from the Universal Protein Resource (UNIPROT) server. The sequence of L-Asparaginase was used to generate 3-D model of L-Asparaginase in SWISS MODEL server. The constructed L-Asparaginase model was verified using Ramachandran Plot in PROCHECK server.Results: The FASTA format of L-Asparaginase enzyme of Bacillus subtilis strain 168 was retrieved from UNIPROT server. The FASTA format of L-Asparaginase was submitted to SWISS MODEL and its three-dimensional structural model was developed based on relevant template model. The model structure of L-Asparaginase was validated in PROCHECK server using Ramachandran Plot. The Ramachandran Plot of L-Asparaginase model inferred the reliability of L-Asparaginase structure model developed in SWISS MODEL server.  Conclusions: In the present study computational tools were exploited to develop and validate a potent anticancer drug, L-Asparaginase. Further the modeled L-Asparaginase enzyme protein can be improved using advanced bioinformatics tools and the same improved enzyme can be produced by improving the L-Asparaginase producing microbial strains by site-directed mutagenesis in the corresponding gene.

scholarly journals Structural model of carnitine palmitoyltransferase I based on the carnitine acetyltransferase crystal

2004 ◽  
Vol 379 (3) ◽  
pp. 777-784 ◽  
Author(s):  
Montserrat MORILLAS ◽  
Eduardo LÓPEZ-VIÑAS ◽  
Alfonso VALENCIA ◽  
Dolors SERRA ◽  
Paulino GÓMEZ-PUERTAS ◽  
...  
Keyword(s):  
Amino Acids ◽  
Structural Model ◽  
Three Dimensional ◽  
Catalytic Efficiency ◽  
Carnitine Palmitoyltransferase ◽  
Carnitine Acetyltransferase ◽  
Catalytic Residues ◽  
Carnitine Palmitoyltransferase I ◽  
Cpt I ◽  
D Model

CPT I (carnitine palmitoyltransferase I) catalyses the conversion of palmitoyl-CoA into palmitoylcarnitine in the presence of l-carnitine, facilitating the entry of fatty acids into mitochondria. We propose a 3-D (three-dimensional) structural model for L-CPT I (liver CPT I), based on the similarity of this enzyme to the recently crystallized mouse carnitine acetyltransferase. The model includes 607 of the 773 amino acids of L-CPT I, and the positions of carnitine, CoA and the palmitoyl group were assigned by superposition and docking analysis. Functional analysis of this 3-D model included the mutagenesis of several amino acids in order to identify putative catalytic residues. Mutants D477A, D567A and E590D showed reduced L-CPT I activity. In addition, individual mutation of amino acids forming the conserved Ser685-Thr686-Ser687 motif abolished enzyme activity in mutants T686A and S687A and altered Km and the catalytic efficiency for carnitine in mutant S685A. We conclude that the catalytic residues are His473 and Asp477, while Ser687 probably stabilizes the transition state. Several conserved lysines, i.e. Lys455, Lys505, Lys560 and Lys561, were also mutated. Only mutants K455A and K560A showed decreases in activity of 50%. The model rationalizes the finding of nine natural mutations in patients with hereditary L-CPT I deficiencies.

scholarly journals Modelling the 2-kinase domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase on adenylate kinase

1997 ◽  
Vol 321 (3) ◽  
pp. 615-621 ◽  
Author(s):  
Luc BERTRAND ◽  
Didier VERTOMMEN ◽  
Eric DEPIEREUX ◽  
Louis HUE ◽  
Mark H. RIDER ◽  
...  
Keyword(s):  
Adenylate Kinase ◽  
Structural Model ◽  
Three Dimensional ◽  
Kinase Domain ◽  
Multiple Alignment ◽  
Site Directed Mutagenesis ◽  
Dimensional Structure ◽  
Conserved Residues ◽  
Nucleotide Binding Proteins ◽  
Sequence Similarities

Simultaneous multiple alignment of available sequences of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase revealed several segments of conserved residues in the 2-kinase domain. The sequence of the kinase domain was also compared with proteins of known three-dimensional structure. No similarity was found between the kinase domain of 6-phosphofructo-2-kinase and 6-phosphofructo-1-kinase. This questions the modelling of the 2-kinase domain on bacterial 6-phosphofructo-1-kinase that has previously been proposed [Bazan, Fletterick and Pilkis (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9642Ő9646]. However, sequence similarities were found between the 2-kinase domain and several nucleotide-binding proteins, the most similar being adenylate kinase. A structural model of the 2-kinase domain based on adenylate kinase is proposed. It accommodates all the results of site-directed mutagenesis studies carried out to date on residues in the 2-kinase domain. It also allows residues potentially involved in catalysis and/or substrate binding to be predicted.

scholarly journals Na3Co2(As0.52P0.48)O4(As0.95P0.05)2O7

2013 ◽  
Vol 69 (12) ◽  
pp. i85-i86 ◽  
Author(s):  
Youssef Ben Smida ◽  
Abderrahmen Guesmi ◽  
Mohamed Faouzi Zid ◽  
Ahmed Driss
Keyword(s):  
Solid State ◽  
Solid State Reaction ◽  
Title Compound ◽  
General Position ◽  
Structural Model ◽  
Three Dimensional ◽  
The Other ◽  
Coordination Polyhedra ◽  
Bond Valence Sum ◽  
Full Occupancy

The title compound, trisodium dicobalt(II) (arsenate/phosphate) (diarsenate/diphosphate), was prepared by a solid-state reaction. It is isostructural with Na3Co2AsO4As2O7. The framework shows the presence of CoX22O12(X2 is statistically disordered with As0.95P0.05) units formed by sharing corners between Co1O6octahedra andX22O7groups. These units form layers perpendicular to [010]. Co2O6octahedra andX1O4(X1 = As0.54P0.46) tetrahedra form Co2X1O8chains parallel to [001]. Cohesion between layers and chains is ensured by theX22O7groups, giving rise to a three-dimensional framework with broad tunnels, running along thea- andc-axis directions, in which the Na+ions reside. The two Co2+cations, theX1 site and three of the seven O atoms lie on special positions, with site symmetries 2 andmfor the Co,mfor theX1, and 2 andm(× 2) for the O sites. One of two Na atoms is disordered over three special positions [occupancy ratios 0.877 (10):0.110 (13):0.066 (9)] and the other is in a general position with full occupancy. A comparison between structures such as K2CdP2O7, α-NaTiP2O7and K2MoO2P2O7is made. The proposed structural model is supported by charge-distribution (CHARDI) analysis and bond-valence-sum (BVS) calculations. The distortion of the coordination polyhedra is analyzed by means of the effective coordination number.

How Simplifying Assumptions Affect the Computation of Three-Dimensional Knee Loads in Cycling

2001 ◽  
Author(s):  
Colin S. Gregersen ◽  
M. L. Hull
Keyword(s):  
Knee Injury ◽  
Knee Injuries ◽  
Three Dimensional ◽  
Simplifying Assumptions ◽  
D Model

Abstract Determining the force and moment components transmitted by the knee is useful both to understand the etiology of over-use knee injuries common in cycling [1] and also to assess how well different interventions protect against over-use injury. Because the loads thought to be primarily responsible for over-use knee injury are the non-driving moments (varus/valgus and internal/external axial moments) transmitted by the knee [2], a 3-D model is necessary for calculating these loads. To our knowledge, no study has developed a model that includes complete 3-D kinematics of the segments to calculate these loads. Consequently one objective of this study was to develop a complete, 3-D model to calculate the intersegmental knee loads during cycling. A second objective was to use this model to examine how simplifying assumptions affect the 3-D knee loads.

3-D Model of Proton Exchange Membrane Fuel Cells

2000 ◽  
Author(s):  
Tianhong Zhou ◽  
Hongtan Liu
Keyword(s):  
Fuel Cell ◽  
Proton Exchange Membrane ◽  
Three Dimensional ◽  
Flow Characteristics ◽  
Pem Fuel Cell ◽  
Proton Exchange ◽  
Three Dimensional Model ◽  
Chemical Reaction Kinetics ◽  
Fuel Cell Performance ◽  
D Model

Abstract A comprehensive three-dimensional model for a proton exchanger membrane (PEM) fuel cell is developed to evaluate the effects of various design and operating parameters on fuel cell performance. The geometrical model includes two distinct flow channels separated by the membrane and electrode assembly (MEA). This model is developed by coupling the governing equations for reactant mass transport and chemical reaction kinetics. To facilitate the numerical solution, the full PEM fuel cell was divided into three coupled domains according to the flow characteristics. The 3-D model has been applied to study species transport, heat transfer, and current density distributions within a fuel cell. The predicated polarization behavior is shown to compare well with experimental data from the literature. The modeling results demonstrate good potential for this computational model to be used in operation simulation as well as design optimization.

scholarly journals Data assimilation for volcanic ash plumes using a satellite observational operator: a case study on the 2010 Eyjafjallajökull volcanic eruption

2017 ◽  
Vol 17 (2) ◽  
pp. 1187-1205 ◽  
Author(s):  
Guangliang Fu ◽  
Fred Prata ◽  
Hai Xiang Lin ◽  
Arnold Heemink ◽  
Arjo Segers ◽  
...  
Keyword(s):  
Data Assimilation ◽  
Volcanic Ash ◽  
Three Dimensional ◽  
Forecast Accuracy ◽  
Improve Model ◽  
Powerful Approach ◽  
Using Data ◽  
D Model

Abstract. Using data assimilation (DA) to improve model forecast accuracy is a powerful approach that requires available observations. Infrared satellite measurements of volcanic ash mass loadings are often used as input observations for the assimilation scheme. However, because these primary satellite-retrieved data are often two-dimensional (2-D) and the ash plume is usually vertically located in a narrow band, directly assimilating the 2-D ash mass loadings in a three-dimensional (3-D) volcanic ash model (with an integral observational operator) can usually introduce large artificial/spurious vertical correlations.In this study, we look at an approach to avoid the artificial vertical correlations by not involving the integral operator. By integrating available data of ash mass loadings and cloud top heights, as well as data-based assumptions on thickness, we propose a satellite observational operator (SOO) that translates satellite-retrieved 2-D volcanic ash mass loadings to 3-D concentrations. The 3-D SOO makes the analysis step of assimilation comparable in the 3-D model space.Ensemble-based DA is used to assimilate the extracted measurements of ash concentrations. The results show that satellite DA with SOO can improve the estimate of volcanic ash state and the forecast. Comparison with both satellite-retrieved data and aircraft in situ measurements shows that the effective duration of the improved volcanic ash forecasts for the distal part of the Eyjafjallajökull volcano is about 6 h.

scholarly journals Reorganization of chromosome architecture in replicative cellular senescence

2016 ◽  
Vol 2 (2) ◽  
pp. e1500882 ◽  
Author(s):  
Steven W. Criscione ◽  
Marco De Cecco ◽  
Benjamin Siranosian ◽  
Yue Zhang ◽  
Jill A. Kreiling ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Structural Model ◽  
Three Dimensional ◽  
Chromatin Accessibility ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
Topologically Associated Domains ◽  
Chromosomal Architecture ◽  
Fundamental Biological Process ◽  
3D Architecture

Replicative cellular senescence is a fundamental biological process characterized by an irreversible arrest of proliferation. Senescent cells accumulate a variety of epigenetic changes, but the three-dimensional (3D) organization of their chromatin is not known. We applied a combination of whole-genome chromosome conformation capture (Hi-C), fluorescence in situ hybridization, and in silico modeling methods to characterize the 3D architecture of interphase chromosomes in proliferating, quiescent, and senescent cells. Although the overall organization of the chromatin into active (A) and repressive (B) compartments and topologically associated domains (TADs) is conserved between the three conditions, a subset of TADs switches between compartments. On a global level, the Hi-C interaction matrices of senescent cells are characterized by a relative loss of long-range and gain of short-range interactions within chromosomes. Direct measurements of distances between genetic loci, chromosome volumes, and chromatin accessibility suggest that the Hi-C interaction changes are caused by a significant reduction of the volumes occupied by individual chromosome arms. In contrast, centromeres oppose this overall compaction trend and increase in volume. The structural model arising from our study provides a unique high-resolution view of the complex chromosomal architecture in senescent cells.

Wave propagation simulation on a 3D model of the Ruhr district for locations of seismic monitoring.

2021 ◽  
Author(s):  
Gabriela de los Angeles Gonzalez de Lucio ◽  
Claudia Finger ◽  
Erik Saenger
Keyword(s):  
Wave Propagation ◽  
Seismic Risk ◽  
Structural Model ◽  
Three Dimensional ◽  
Seismic Source ◽  
Industrial Area ◽  
Structural Features ◽  
Maximum Energy ◽  
Seismic Events ◽  
Ruhr District

<p>The Ruhr district meets the necessary elements to carry out geothermal projects due to its geothermal potential and demand, as it is a densely populated industrial area. Currently, there are projects for direct use, whereas projects for electricity generation are planned. The latter, due to greater depths, reservoir enhancement techniques are required in some cases. This may increase the associated seismic risk which should be elaborated in detail.</p><p>With available data, a three-dimensional geological and structural model was created. The shallower parts have been widely studied and documented by mining activity in the Ruhr region during the last century.  Below a depth of 1 km, data are scarce, and uncertainties increase. The full elastic wavefield emitted by a realistic seismic source has been simulated using a finite differences scheme and the derived geological model. The elastic properties were estimated with well data. The source has common characteristics of real seismic events in the area.</p><p>The wave propagation simulations let us analyze the seismic response with different sources and velocities models. Three cases are considered, two seismic events with distinct depths based on real events. The third case is based on the proposed location of a deep geothermal project.</p><p>Especially for the case with the deeper source, the areas with relatively high amplitudes of displacement correlated with structural features of the model. Applying the imaging condition of maximum energy density allows us to define zones with a potentially increased seismic risk that should be monitored more closely.</p>

A Scalable Time-Parallel Solution of Periodic Rotor Dynamics in X3D

2021 ◽  
Author(s):  
Mrinalgouda Patil ◽  
Anubhav Datta
Keyword(s):  
Harmonic Balance ◽  
Large Scale ◽  
Structural Model ◽  
Three Dimensional ◽  
Harmonic Balance Method ◽  
Flight Test ◽  
Solution Procedure ◽  
Balance Method ◽  
Computational Time ◽  
Near Resonance

A time-parallel algorithm is developed for large-scale three-dimensional rotor dynamic analysis. A modified harmonic balance method with a scalable skyline solver forms the kernel of this algorithm. The algorithm is equipped with a solution procedure suitable for large-scale structures that have lightly damped modes near resonance. The algorithm is integrated in X3D, implemented on a hybrid shared and distributed memory architecture, and demonstrated on a three-dimensional structural model of a UH-60A-like fully articulated rotor. Flight-test data from UH-60A Airloads Program transition flight C8513 are used for validation. The key conclusion is that the new solver converges to the time marching solution more than 50 times faster and achieves a performance greater than 1 teraFLOPS. The significance of this conclusion is that the principal barrier of computational time for trim solution using high-fidelity three-dimensional structures can be overcome with the scalable harmonic balance method demonstrated in this paper.

Development of an Interactive Virtual 3-D Model of the Human Testis Using the Second Life Platform

2012 ◽  
pp. 153-167
Author(s):  
Douglas R. Danforth
Keyword(s):  
Second Life ◽  
Three Dimensional ◽  
Human Testis ◽  
Anatomy And Physiology ◽  
Organ Systems ◽  
Life Context ◽  
Cellular Modeling ◽  
Primary Focus ◽  
D Model ◽  
Pedagogical Approaches

One of the strengths of a virtual environment is the ability to immerse the occupant into an environment that would otherwise be impossible. The primary focus of the author’s project in Second Life is to take advantage of this opportunity to explore novel approaches to medical education. Second Life can be used to model doctor-patient interaction, clinical diagnosis skills, and three dimensional molecular and cellular modeling of objects from individual molecules to whole organ systems, both healthy and diseased. Using the powerful building and scripting tools of the Second Life platform, the author has created a model of the human testis that students can fly through and interact with to understand how the anatomy and physiology of the testis work together to regulate sperm production. The anatomical and physiological interactions occurring during these processes are described in accompanying audio and text. The development of educational tools within the Second Life context is in its infancy. As the technology matures, the opportunities for education within Second Life will continue to expand as an important adjunct to traditional pedagogical approaches.

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