ISRN Computational Biology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. In Silico Proteome Cleavage Reveals Iterative Digestion Strategy for High Sequence Coverage Tue, 22 Apr 2014 09:11:33 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2014/960902/ In the postgenome era, biologists have sought to measure the complete complement of proteins, termed proteomics. Currently, the most effective method to measure the proteome is with shotgun, or bottom-up, proteomics, in which the proteome is digested into peptides that are identified followed by protein inference. Despite continuous improvements to all steps of the shotgun proteomics workflow, observed proteome coverage is often low; some proteins are identified by a single peptide sequence. Complete proteome sequence coverage would allow comprehensive characterization of RNA splicing variants and all posttranslational modifications, which would drastically improve the accuracy of biological models. There are many reasons for the sequence coverage deficit, but ultimately peptide length determines sequence observability. Peptides that are too short are lost because they match many protein sequences and their true origin is ambiguous. The maximum observable peptide length is determined by several analytical challenges. This paper explores computationally how peptide lengths produced from several common proteome digestion methods limit observable proteome coverage. Iterative proteome cleavage strategies are also explored. These simulations reveal that maximized proteome coverage can be achieved by use of an iterative digestion protocol involving multiple proteases and chemical cleavages that theoretically allow 92.9% proteome coverage. Jesse G. Meyer Copyright © 2014 Jesse G. Meyer. All rights reserved. Application of Hybrid Functional Groups to Predict ATP Binding Proteins Wed, 08 Jan 2014 11:15:19 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2014/581245/ The ATP binding proteins exist as a hybrid of proteins with Walker A motif and universal stress proteins (USPs) having an alternative motif for binding ATP. There is an urgent need to find a reliable and comprehensive hybrid predictor for ATP binding proteins using whole sequence information. In this paper the open source LIBSVM toolbox was used to build a classifier at 10-fold cross-validation. The best hybrid model was the combination of amino acid and dipeptide composition with an accuracy of 84.57% and Mathews Correlation Coefficient (MCC) value of 0.693. This classifier proves to be better than many classical ATP binding protein predictors. The general trend observed is that combinations of descriptors performed better and improved the overall performances of individual descriptors, particularly when combined with amino acid composition. The work developed a comprehensive model for predicting ATP binding proteins irrespective of their functional motifs. This model provides a high probability of success for molecular biologists in predicting and selecting diverse groups of ATP binding proteins irrespective of their functional motifs. Andreas N. Mbah Copyright © 2014 Andreas N. Mbah. All rights reserved. All Phase Resetting Curves Are Bimodal, but Some Are More Bimodal Than Others Thu, 12 Dec 2013 11:28:27 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/230571/ Phase resetting curves (PRCs) are phenomenological and quantitative tools that tabulate the transient changes in the firing period of endogenous neural oscillators as a result of external stimuli, for example, presynaptic inputs. A brief current perturbation can produce either a delay (positive phase resetting) or an advance (negative phase resetting) of the subsequent spike, depending on the timing of the stimulus. We showed that any planar neural oscillator has two remarkable points, which we called neutral points, where brief current perturbations produce no phase resetting and where the PRC flips its sign. Since there are only two neutral points, all PRCs of planar neural oscillators are bimodal. The degree of bimodality of a PRC, that is, the ratio between the amplitudes of the delay and advance lobes of a PRC, can be smoothly adjusted when the bifurcation scenario leading to stable oscillatory behavior combines a saddle node of invariant circle (SNIC) and an Andronov-Hopf bifurcation (HB). Sorinel A. Oprisan Copyright © 2013 Sorinel A. Oprisan. All rights reserved. Impact of Intravenous Drug Use on HIV/AIDS among Women Prisoners: A Mathematical Modelling Approach Thu, 12 Dec 2013 10:39:16 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/718039/ Intravenous drug use and tattooing remain one of the major routes of HIV/AIDS transmission among prisoners. We formulate and analyze a deterministic model for the role of intravenous drug use in HIV/AIDS transmission among women prisoners. With the aid of the Centre Manifold theory, the endemic equilibrium is shown to be locally asymptotically stable when the corresponding reproduction number is greater than unity. Analysis of the reproduction number and numerical simulations suggest that an increase in intravenous drug use among women prisoners as they fail to cope with prison settings fuels the HIV/AIDS epidemic in women prisoners. Failure to control HIV/AIDS among female prisoners may be a time bomb to their communities upon their release. Thus, it may be best to consider free needle/syringe exchange and drug substitution treatment programmes in women prisons as well as considering open prison systems for less serious crimes. C. P. Bhunu and S. Mushayabasa Copyright © 2013 C. P. Bhunu and S. Mushayabasa. All rights reserved. A Reduced Drosophila Model Whose Characteristic Behavior Scales Up Thu, 14 Nov 2013 09:01:14 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/756829/ Computational biology seeks to integrate experimental data with predictive mathematical models—testing hypotheses which result from the former through simulations of the latter. Such models should ideally be approachable and accessible to the widest possible community, motivating independent studies. One of the most commonly modeled biological systems involves a gene family critical to segmentation in Drosophila embryogenesis—the segment polarity network (SPN). In this paper, we reduce a celebrated mathematical model of the SPN to improve its accessibility; unlike its predecessor our reduction can be tested swiftly on a widely used platform. By reducing the original model we identify components which are unnecessary; that is, we begin to detect the core of the SPN—those mechanisms that are essentially responsible for its characteristic behavior. Hence characteristic behavior can scale up; we find that any solution of our model (defined as a set of conditions for which characteristic behavior is seen) can be converted into a solution of the original model. The original model is thus made more accessible for independent study through a more approachable reduction which maintains the robustness of its predecessor. Andrew David Irving Copyright © 2013 Andrew David Irving. All rights reserved. Zebra Finch Glucokinase Containing Two Homologous Halves Is an In Silico Chimera Thu, 07 Nov 2013 16:35:40 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/790240/ Chimerical nature of the gene annotated as Zebra finch (Taeniopygia guttata) glucokinase (hexokinase IV) has been proved in this study. N-half of the protein encoded by that gene shows similarity with glucokinase from other vertebrates, while its C-half shows similarity with C-halves of hexokinases II. We mapped 7 new exons coding for N-half of hexokinase II and 4 new exons coding for glucokinase of Zebra finch. Finally, we reconstructed normal genes coding for Zebra finch glucokinase and hexokinase II which are situated in “head-to-tail” orientation on the chromosome 22. Because of the error in gene annotation, exons encoding N-half of normal glucokinase have been fused with exons encoding C-half of normal hexokinase II, even though they are separated from each other by the sequence 98066 nucleotides in length. Khrustalev Vladislav Victorovich, Lelevich Sergey Vladimirovich, and Barkovsky Eugene Victorovich Copyright © 2013 Khrustalev Vladislav Victorovich et al. All rights reserved. Text Mining Perspectives in Microarray Data Mining Tue, 05 Nov 2013 10:24:24 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/159135/ Current microarray data mining methods such as clustering, classification, and association analysis heavily rely on statistical and machine learning algorithms for analysis of large sets of gene expression data. In recent years, there has been a growing interest in methods that attempt to discover patterns based on multiple but related data sources. Gene expression data and the corresponding literature data are one such example. This paper suggests a new approach to microarray data mining as a combination of text mining (TM) and information extraction (IE). TM is concerned with identifying patterns in natural language text and IE is concerned with locating specific entities, relations, and facts in text. The present paper surveys the state of the art of data mining methods for microarray data analysis. We show the limitations of current microarray data mining methods and outline how text mining could address these limitations. Jeyakumar Natarajan Copyright © 2013 Jeyakumar Natarajan. All rights reserved. Effective Single-Step Posttranscriptional Dynamics Allowing for a Direct Maximum Likelihood Estimation of Transcriptional Activity and the Quantification of Sources of Gene Expression Variability with an Illustration for the Hypoxia and TNFα Regulated Inflammatory Pathway Mon, 09 Sep 2013 13:41:41 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/719138/ Data analysis methods for estimating promoter activity from gene reporter data frequently involve the reconstruction of the dynamics of unobserved species and numerical search algorithms for determining optimal model parameters. In contrast, we argue that posttranscriptional dynamics effectively behave like a singlestep stochastic process when gene expression variability is relatively low and, half-lives of the unobserved species are relatively small compared to characteristic observation time scales. In this case, by means of maximum likelihood estimators, for which analytical expressions exist, transcriptional activity of gene promoters can be estimated directly from observed gene reporter data without the need for numerical search algorithms and the reconstruction of unobserved variables. In addition, the model-based data analysis approach yields a single variable that measures the effective strength of the sources that give rise to gene expression variability. The approach is applied to conduct a model-based analysis of the inflammatory pathway under hypoxia condition and stimulation with tumor necrosis factor alpha in HEK293 cells. T. D. Frank, A. J. F. Collins, and A. Cheong Copyright © 2013 T. D. Frank et al. All rights reserved. Propagation of Nonlinear Pressure Waves in Blood Tue, 06 Aug 2013 10:32:07 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/436267/ The propagation of weakly nonlinear pressure waves in a fluid-filled elastic tube has been investigated. The reductive perturbation method has been employed to derive the Korteweg-de Vries equation for small but finite amplitude. The effect of the final inner radius of the tube on the basic properties of the soliton wave was discussed. Moreover, the conditions of stability and the soliton existence via the potential and the corresponding phase portrait were computed. The applicability of the present investigation to flow problems in arteries is discussed. A. Elgarayhi, E. K. El-Shewy, Abeer A. Mahmoud, and Ali A. Elhakem Copyright © 2013 A. Elgarayhi et al. All rights reserved. A Whole Genome Pairwise Comparative and Functional Analysis of Geobacter sulfurreducens PCA Wed, 24 Jul 2013 13:24:59 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/850179/ Geobacter species are involved in electricity production, bioremediations, and various environmental friendly activities. Whole genome comparative analyses of Geobacter sulfurreducens PCA, Geobacter bemidjiensis Bem, Geobacter sp. FRC-32, Geobacter lovleyi SZ, Geobacter sp. M21, Geobacter metallireducens GS-15, Geobacter uraniireducens Rf4 have been made to find out similarities and dissimilarities among them. For whole genome comparison of Geobacter species, an in-house tool, Geobacter Comparative Genomics Tool (GCGT) has been developed using BLASTALL program, and these whole genome analyses yielded conserved genes and they are used for functional prediction. The conserved genes identified are about 2184 genes, and these genes are classified into 14 groups based on the pathway information. Functions for 74 hypothetical proteins have been predicted based on the conserved genes. The predicted functions include pilus type proteins, flagellar proteins, ABC transporters, and other proteins which are involved in electron transfer. A phylogenetic tree from 16S rRNA of seven Geobacter species showed that G. sulfurreducens PCA is closely related to G. metallireducens GS-15 and G. lovleyi SZ. For evolutionary study, acetate kinase protein is used, which showed closeness to Pelobacter propionicus, Pelobacter carbinolicus, and Deferribacteraceae family bacterial species. These results will be useful to enhance electricity production by using biotechnological approaches. Ashok Selvaraj, Subazini Thankaswamy Kosalai, Rajadurai Chinnasamy Perumal, Subhashini Pitchai, and Gopal Ramesh Kumar Copyright © 2013 Ashok Selvaraj et al. All rights reserved. Cystathionine β-Lyase-Like Protein with Pyridoxal Binding Domain Characterized in Leishmania major by Comparative Sequence Analysis and Homology Modelling Thu, 18 Jul 2013 08:30:17 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/520435/ Cystathionine β-lyase-like protein (CBLP), one of the key enzymes involved in methionine biosynthesis utilising pyridoxal phosphate (PLP) as a cofactor, has recently been reported in Leishmania major. Its presence in the parasite and absence in humans warrant its full characterisation and fruition as a potent, selective, and inevitable druggable target. Due to the unavailability of X-ray 3D structure of CBLP, a homology model for this protein was developed for the first time. The model was evaluated for PLP binding site and various conserve domain residues of the protein recommended by comparative sequence analyses by different protein analysis tools. The model was validated and discovered to be robust and statistically significant. The final model was superimposed on template of Arabidopsis thaliana (PDB ID: 1IBJ) and RMSD was found to be 0.486. The PLP binding site residues of both the proteins were ensued to be highly conserved indicated by Gly71, Met72, Tyr95, Asp169, and Ser193 as well as formation of aldimine bond with Lys194. This was further verified through molecular simulation of PLP into the cofactor binding site of the modelled protein. The present study may therefore play a directing role in the designing of novel, potential, and selective antileishmanial agents. Arvind Negi, Satej Bhushan, Pawan Gupta, Prabha Garg, and Raj Kumar Copyright © 2013 Arvind Negi et al. All rights reserved. The P25 Ookinete Surface Proteins: Homology Modeling and Phylogenetic Relationships Tue, 14 May 2013 14:32:08 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/391018/ Sexual stages of Plasmodium such as zygote, ookinete, and young oocysts express 25 kDa surface protein P25, which along with P28 proteins protect the parasite from harmful environment inside mosquito midgut. Vaccines against these proteins induce antibodies in vertebrate host capable to inhibit parasite development in mosquito midgut and thus preventing the transmission of parasite from mosquito to other human host. Transmission-blocking vaccines help reduce malaria burden. The purpose of this study was in silico structural characterization of P25 family proteins and to predict their phylogenetic relationships with other proteins. Results indicate that members of P25 family have four EGF domains arranged in triangular fashion with major variations lying in the loop regions. All 22 cysteines are conserved forming 11 disulphide bonds. The C-loop of EGF domain IV in P25 proteins is smaller in comparison to P28 proteins. B loop of EGF domain II showed maximum RMSD variations followed by loops of EGF domain III. P25 proteins are tile-like triangular flat proteins that protect the parasite inside mosquito midgut. Obtained structures will help in understanding the biology of the parasite inside the mosquito midgut. These structures may also help in designing transmission-blocking vaccine against malaria in absence of experimentally determined structures. Babita Sharma and Manoj Kumar Jaiswal Copyright © 2013 Babita Sharma and Manoj Kumar Jaiswal. All rights reserved. HomoKinase: A Curated Database of Human Protein Kinases Mon, 22 Apr 2013 10:47:45 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/417634/ HomoKinase database is a comprehensive collection of curated human protein kinases and their relevant biological information. The entries in the database are curated by three criteria: HGNC approval, gene ontology-based biological process (protein phosphorylation), and molecular function (ATP binding and kinase activity). For a given query protein kinase name, the database provides its official symbol, full name, other known aliases, amino acid sequences, functional domain, gene ontology, pathways assignments, and drug compounds. In addition, as a search tool, it enables the retrieval of similar protein kinases with specific family, subfamily, group, and domain combinations and tabulates the information. The present version contains 498 curated human protein kinases and links to other popular databases. Suresh Subramani, Saranya Jayapalan, Raja Kalpana, and Jeyakumar Natarajan Copyright © 2013 Suresh Subramani et al. All rights reserved. Saving Significant Amount of Time in MD Simulations by Using an Implicit Solvent Model and Elevated Temperatures Sun, 31 Mar 2013 09:59:40 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/640125/ Molecular dynamic simulations are used for investigating various aspects of biological processes. Such simulations often require intensive computer power; therefore several solutions were developed to minimize the computer power needed, including the usage of elevated temperatures. Yet, such simulations are still not commonly used by the wide scientific community of chemists and biochemists. For about two years now, the molecular simulations suite GROMACS enables conducting simulations using implicit solvent models to further decrease runtimes. In order to quantify the saving in computer power, and to confirm the validity of the models, we followed the simple dissolution process of a single NaCl molecule. The results reveal approximately 350-fold decrease in real-world runtime when using an implicit solvent model and an elevated temperature, compared to using explicit water molecules and simulating at room temperature. In addition, in a wide range of temperatures, the dissolution times of NaCl are distributed, as expected, exponentially, both in explicit and in implicit solvent models, hence confirming the validity of the simulation approach. Hopefully, our findings will encourage many scientists to take advantage of the recent progress in the molecular dynamics field for various applications. Ifat Shub, Ehud Schreiber, and Yossef Kliger Copyright © 2013 Ifat Shub et al. All rights reserved. Assessing the Impact of Vaccination on Controlling the Spread of Human Scabies Thu, 28 Mar 2013 18:31:37 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/362973/ Scabies is among the infestations almost forgotten due to its association with poor communities. We formulate a deterministic model to assess the possible impact vaccination will have on scabies control. The Descartes’s rule of signs is used to show the nature of the endemic equilibria. Analysis of the reproduction number and numerical simulations suggest that vaccination in addition to treatment will help greatly in reducing the spread of scabies infestation. This suggests there is a strong need for researchers to come up with a possible vaccine in that order to effectively control scabies especially among the disadvantaged communities. C. P. Bhunu, S. Mushayabasa, and T. G. Monera Copyright © 2013 C. P. Bhunu et al. All rights reserved. Molecular Docking and Quantum Mechanical Studies on Pelargonidin-3-Glucoside as Renoprotective ACE Inhibitor Thu, 28 Mar 2013 13:56:55 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/428378/ Background and Aim. Despite tangible progress in recent years, substantial therapeutic challenges remain unexplored in nephropathy, particularly in diabetic patient. Addressing these challenges requires identification of novel drugs and development of noninvasive and cost-effective methods to select the most appropriate therapeutic option for the disease. Angiopathic nephropathy is one of the complications of diabetes mellitus and is becoming the single most important reason for end-stage renal disease in the western world. This study has investigated the inhibitory effect of a library naturally occurring nonprotein compounds that inhibit angiotensin converting enzyme (ACE). Materials and Methods. Docking studies of ACE protein with natural compounds and synthetic commercial drug perindopril were done using AutoDock, FlexX, and Hex. Toxicity predictions were carried out using OpenTox. Quantum mechanical properties were studied using GAMESS. Results. Pelargonidin-3-glucoside could be used as a potent renoprotective drug candidate, which inhibits ACEII. It has low toxicity and its quantum mechanical properties are comparable to those of commercial drugs. Talambedu Usha, Pranav Tripathi, Veena Pande, and Sushil Kumar Middha Copyright © 2013 Talambedu Usha et al. All rights reserved. The ABCs of Experimental Evolution Thu, 07 Mar 2013 11:17:56 +0000 http://www.hindawi.com/journals/isrn.computational.biology/2013/467943/ Microbial evolution is complex and is influenced by many sources of variation. Experimental evolution is no exception, although it is more controlled, easily replicated, and typically devoid of interactions between species. Mathematical modeling of the evolutionary process can help in understanding the underlying mechanisms that drive outcome of such experiments. These models can be complex and parameter rich, limiting their feasibility for statistical inference. In this paper, we introduce the use of Approximate Bayesian Computation (ABC) as a tool for statistical inference in the study of experimental evolution. ABC is a fast and simple method for fitting complex models to data. We utilize this method, coupled with a mechanistic model of experimental evolution, to study the evolution process of bacteriophage ϕX174 under benign selection pressure. Our results highlight three mutation-selection scenarios that could explain this process: high mutation/low selection pressure, low mutation/high selection pressure, and low mutation/low selection pressure, with posterior support of 19%, 9.5%, and 71.5% for each of these scenarios, respectively. Sequence data support the first candidate. Though surprising, this scenario was not improbable based on our analysis. Zaid Abdo, Mathew Stein, Andrzej Wojtowicz, and Kim M. Pepin Copyright © 2013 Zaid Abdo et al. All rights reserved.