International Journal for Computational Biology (IJCB)
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Exploring the pre-erythrocytic stage of the malaria parasite for possible target proteins to develop an effective vaccine and looking into available preventive measures against malaria:Can SPECT & SPECT2 act as potential targets for an effective vaccine?
Get PDFMalaria is most commonly found in tropical and sub-tropical countries of Africa. In a year, 3.2 billion people are at risk of getting malaria of which infection occurs in over 200 million of which one million results in death; hence it is one of the most infectious parasite diseases. 90% of the deaths occur in south of Saharan desert and most of the cases are of children under the age of five. In the year 2012, malaria caused estimated total deaths of 627,000. In the year 2013, malaria caused estimated total deaths of 500,000. 40% of total malaria cases in the world are from Nigeria and the Democratic Republic of Congo (Statistics provided by WHO). These stats strongly suggest the need of a preventive malaria vaccine. Here we analyze the malaria parasite cycle, specifically pre-erythrocytic stage, and present some possible target proteins. We also look at the current options for prevention of malaria
Insilico Drug Prediction and Validation of Lead candidates on Plasmodium falciparum Erythrocyte Membrane Protein 1(pfEMP1) against Malaria
Get PDFMalaria is an infectious disease caused by protozoan of the genus Plasmodium. It is transmitted by bite from infected female Anopheles mosquito. Plasmodium falciparum erythrocyte membrane protein 1 (PfEmp1), an antigen that is responsible for the immune evasion of the protozoan. This protein has adhesive properties that cause the infected erythrocytes to bind to the endothelial lining of the blood vessel, thus preventing the infected cells from getting filtered by the spleen. It is found that there is an interaction between the sulphate ion on the endothelial cells and NH1, NH2 of Arg 1467 (A), NZ of Lys 1324 (A) and two bonds with N of Gly 1329 (A) on the protein. Inhibiting this interaction may prevent the evasive action. A Ligand with SO4 interactive region can be used to achieve this. Computer aided drug designing techniques were used to find a new scaffold to solve the purpose. GROMACS was used to simulate the protein-Ligand interaction. It was observed that ZINC17206599 shows the best interaction and may prove to be a promising candidate drug for Malaria.
Recent Trends in In-silico Drug Discovery
Get PDFA Drug designing is a process in which new leads (potential drugs) are discovered which have therapeutic benefits in diseased condition. With development of various computational tools and availability of databases (having information about 3D structure of various molecules) discovery of drugs became comparatively, a faster process. The two major drug development methods are structure based drug designing and ligand based drug designing. Structure based methods try to make predictions based on three dimensional structure of the target molecules. The major approach of structure based drug designing is Molecular docking, a method based on several sampling algorithms and scoring functions. Docking can be performed in several ways depending upon whether ligand and receptors are rigid or flexible. Hotspot grafting, is another method of drug designing. It is preferred when the structure of a native binding protein and target protein complex is available and the hotspots on the interface are known. In absence of information of three Dimensional structure of target molecule, Ligand based methods are used. Two common methods used in ligand based drug designing are Pharmacophore modelling and QSAR. Pharmacophore modelling explains only essential features of an active ligand whereas QSAR model determines effect of certain property on activity of ligand. Fragment based drug designing is a de novo approach of building new lead compounds using fragments within the active site of the protein. All the candidate leads obtained by various drug designing method need to satisfy ADMET properties for its development as a drug. In-silico ADMET prediction tools have made ADMET profiling an easier and faster process. In this review, various softwares available for drug designing and ADMET property predictions have also been listed
Determination of Metabolic pathways and PPI network of Sarigol in Response to Osmotic stress: An in silico study
Get PDFThe complexity of plants response to abiotic stress make difficult to manage and target special genes/proteins to be used in improving crop performance. Therefore, understanding and insight into molecular mechanisms recruited by plants under stressful conditions is essence. In this aim, Sarigol, a salt-sensitive cultivar of canola, based on their differentially expressed proteins was studied in silico. The results indicated that the majority of proteins had molecular function of catalytic activity and involvement of these proteins in response to stress underrepresented by Sarigol, whereas proteins involved in cellular and metabolic process were overrepresented. Phylogenetic analysis divided the proteins into 4 groups and protein-protein interaction network prediction illustrated two sets of interacted proteins, while most of proteins did not show any interactions. The results suggested that in the molecular level, Sarigol is unable to respond appropriate actions as are observed in tolerant plants.
Flexibility analysis of Native Pyridoxal Kinase and its complexes with ATP and ADP: A Molecular Dynamics Simulation Study
Get PDFPyridoxal Kinase (PLK) phosphorylates vitamin B6, a step required for the conversion of Vitamin B6 into pyridoxal 5-phosphate. The protein is cytoplasmic and is active as a dimer. Molecular dynamics (MD) simulation studies using a 25ns scale for PLK and its complex with ATP (Adenosine triphosphate) and ADP (Adenosine diphosphate) were carried out and the trajectory analysis revealed that the flexibility of the entire PLK molecule increases. In present study we have investigated the conformational changes in pyridoxal kinase (PLK) after binding of ligands (ATP/ADP). The stability of native and PLK in complex with ATP and ADP, was ascertained by MD simulations and mechanism of ligand binding was explored by essential dynamics. Simulation results also indicated that the van der Waals contribution was greater than the electrostatic interaction between the protein residues and the ligands. Further, the ligand (ATP/ADP) binding results into decrement and increment of fluctuations in certain regions of protein.
Molecular dynamics and Conformational flexibility in Heat Shock Protein 60.2 of Mycobacterium tuberculosis
Get PDFHSP 60.2 plays important role in pathogenesis of Mycobacterium tuberculosis causing tuberculosis. This chaperonin comprises of three domains namely-apical, intermediate and equatorial which assists in proper protein folding thus preventing aggregation of unfolded polypeptides. To evaluate the structural changes during protein folding, conformations of HSP 60.2 were monitored during 10 ns time scale. Molecular dynamic simulations are used to study the large amount of molecular and biomolecular conformations with the use of high end computational assistance. The Principal component analysis and clustering techniques are used for revealing major conformational changes that occur in the MD simulation. Normal mode analysis was also performed to study the conformation and direction of motion of a protein under study for a large time scale simulation. These studies suggest that functional behavior of protein that depends on the structure. Chaperonin 60.2 is not only plays a role as protein folding machinery, but also an immunologically important biomolecule. Hence it is provided and drawn a clear path between role of chaperon in protein folding and their role in the infection showing the immunological importance of Heat Shock Protein 60.2
DEN: an R-Bioconductor based package to extract active sub-networks from human interaction map by integrating gene-expression data
Get PDFLiving cells are complex, dynamic, self-regulatory, interactive systems, showing differential states across time and space. Complexity of cellular systems is highlighted with the multi-layered regulatory mechanisms involving the interactions between bio-molecules (such as DNA, RNA, mi-RNA and proteins). These interactions are analyzed in the form of static networks. Likewise, number of experimental techniques like microarray, RNASeq allow quantification of cellular dynamics and aid in discerning differential gene expression across diverse conditions. Computational biology is in need of methods for integration of static networks and gene expression data, since it provides interesting insights into the dynamics of biological systems. DEN is an R/Bioconductor based package designed to assemble different types of human bio-molecular interactions as a complete interactome and contains functions to extract dynamic active networks by integration of gene expression data
Comparative Study of Homology Based Structure Prediction and Structure Validation Tools on Some Proteins from the bhlh family.
Get PDFComparative homology modeling has become an efficient and easy method for predicting the unknown three dimensional structure of a protein based on sequence alignment. The steps involved are template alignment, loop assignment, model building and model refinement. However, it was noticed that though the basic steps for modeling the protein was same, the results produced by different tools that is available varied, possibly due to the efficiency of the algorithm and other factors. Here, five homology modelling tools were used to compare the results for some proteins of the bhlh family. It was also noticed that structure validation tools had different results. To compare the results ProcheckRamchandran plot from PDBSum Generate and Ramchandran plot from SPDBV were used. The differing results were compared using simple statistical approach and the inference was obtained as patterns for the tools
Identification of Salmonella Strains of Phyllosphere Food Poisoning by Melt Curve Analysis: In Silico approach
Get PDFDuring last few decades, there have been increased incidences of outbreak of diseases due to consumption of fresh vegetables and fruits contaminated with human pathogens. Such threats warrant rapid detection test. The standard method of diagnosis relies on culture-plate and serological methods which lack discrimination and are time consuming having several drawbacks, inconsistency and are less efficient. We applied bioinformatics approaches to develop of a real- time PCR simulation for detecting Salmonella serovars which are involved in most disease outbreaks associated with phyllosphere. Salmonella enterica subspecies enterica (designated as S. enterica) are common in plants, on surface as well as present internally in tissues. Though more than 2500 serovars of Salmonella enterica are known but the reports of serovars colonizing in plants are limited. Nucleotide sequence variation in target genes, viz. PurE, SucA, hisD, hivA and fliC were used in in silico to differentiate Salmonella serovars. A large number of reference sequences of target genes were retrieved from NCBI, and common conserved region were used for development of multiplex primer design using muPlex. Primer thermodynamic properties and secondary structure were assessed using Beacon designer. Sequences were truncated to remove sequences outside of the region bounded by the primers. We performed in silico DNA melting simulations with several Salmonella serovars using the programs umelt, and tested the utility of the programs for assay design, which will save time and cost of in vitro testing several multiple primers in RT PCR.Keywords- In Silico; Salmonella ; Phyllosphere;Real-time PCR (RT-PCR