In Silico Biology - Volume 7, issue 2

Authors: Gayen, Kalyan | Gupta, Manish | Venkatesh, Kareenhalli V.

Article Type: Research Article

Abstract: Quantification of metabolism through elementary modes offers insights into the working of a metabolic network. We have determined the fluxes of elementary modes through linear optimization using the stoichiometry of the elementary modes as a constraint. We apply this methodology to obtain insights into the effect of preculturing on growth of Lactobacillus rhamnosus on medium containing mixed substrates. L. rhamnosus, a microaerophilic organism, produces flavor compounds such as diacetyl and acetoin during growth …on glucose and citrate. The uptake of citrate has been shown to be sensitive to preculturing states of the cells. Elementary modes demonstrated that citrate was utilized by the organism as a sole carbon source. Further, both glucose and citrate was catabolized by this organism through aerobic and anaerobic routes. The flux analysis indicated that only 21 elementary modes were operational during growth of L. rhamnosus on glucose and citrate. Glucose specifically accounted for 6 elementary modes, while the remaining 15 involved citrate as substrate. The modes associated with glucose were mainly operational when cells were precultured on glucose. It was observed that all the 21 modes contributed to the fluxes when the cells were precultured on citrate. The NADH recycling through lactate formation and oxygen uptake were dependent on the preculturing state. The analysis also demonstrated that preculturing on citrate yielded better productivity of diacetyl and acetoin. Show more

Keywords: Elementary modes, linear optimization, Lactobacillus rhamnosus, flavor production, preculturing state

Citation: In Silico Biology, vol. 7, no. 2, pp. 123-139, 2007

Authors: Negishi, Yoshiteru | Nakamura, Hiroyuki | Yachie, Nozomu | Saito, Rintaro | Tomita, Masaru

Article Type: Research Article

Abstract: Analysis and visualization of biological networks, such as protein-protein and protein-DNA interactions, are crucially important toward obtaining a thorough understanding of living systems. Here, we present an integrative software platform, eXpanda, which enables an analysis of a very broad range of biological networks, with a special focus on the extraction of characteristic topologies which potentially function as units in the networks. eXpanda is provided as a Perl library which gives full-automatic connections to …various biological databases via a Perl programmable interface and can perform topological analysis based on graph theory. The results of these analyses are visualizable by vector graphics. eXpanda is under GNU General Public License. Software package, detailed documentations, source codes, and some sample scripts are downloadable at http://medcd.iab.keio.ac.jp/expanda/. Show more

Keywords: Interactome, network analysis, network visualization, Perl library, Scalable Vector Graphics (SVG)

Citation: In Silico Biology, vol. 7, no. 2, pp. 141-144, 2007

Authors: Fink, J. Lynn | Hamilton, Nicholas

Article Type: Research Article

Abstract: Visualization of functional and structural features of biological macromolecules is an important aspect of communicating and analyzing biological data, for example the presence of a transmembrane domain in relation to a nucleotide binding site or the organization of transcription factor binding sites in a promoter. However, this is not necessarily a trivial task especially when the feature information is complex or lengthy. While there are some tools available that can create these images, none have been …implemented for the specific purpose of automating the generation of presentation-quality graphics for displaying feature information. We have implemented DomainDraw, a visualization tool that can be used to generate schematic diagrams of biological macromolecules for the purpose of representing the relative position and range of user-specified domains or motifs. The user specifies the name, position, and range of the domains of interest and DomainDraw generates the image based on these parameters. Optional parameters include domain color and shape, image size, and whether to align multiple proteins using a particular domain. DomainDraw is publicly available as a web server and can be accessed at http://domaindraw.imb.uq.edu.au. The executable may be obtained by contacting the authors. Show more

Keywords: Visualization, functional genomics, high-throughput methods

Citation: In Silico Biology, vol. 7, no. 2, pp. 145-150, 2007

Authors: Gerlach, Daniel | Wolf, Matthias | Dandekar, Thomas | Müller, Tobias | Pokorny, Andreas | Rahmann, Sven

Article Type: Research Article

Abstract: We reconstructed a robust phylogenetic tree of the Metazoa, consisting of almost 1,500 taxa, by profile neighbor joining (PNJ), an automated computational method that inherits the efficiency of the neighbor joining algorithm. This tree supports the one proposed in the latest review on metazoan phylogeny. Our main goal is not to discuss aspects of the phylogeny itself, but rather to point out that PNJ can be a valuable tool when the basal branching pattern of a …large phylogenetic tree must be estimated, whereas traditional methods would be computationally impractical. Show more

Keywords: 18S rRNA, animals, Articulata, bootstrap, Coelomata, Deuterostomia, Ecdysozoa, large tree, Lophotrochozoa, Metazoa, phylogenetics, phylogeny, Platyzoa, PNJ, probabilistic sequence profile, ProfDist, profile neighbor-joining, supertree method, systematics

Citation: In Silico Biology, vol. 7, no. 2, pp. 151-154, 2007

Authors: Ahmed, Ahmed | Frey, Gabriel | Michel, Christian J.

Article Type: Research Article

Abstract: Three sets of 20 trinucleotides are preferentially associated with the reading frames and their 2 shifted frames of both eukaryotic and prokaryotic genes. These 3 sets are circular codes. They allow retrieval of any frame in genes (containing these circular code words), locally anywhere in the 3 frames and in particular without start codons in the reading frame, and automatically with the reading of a few nucleotides. The circular code in the reading frame, noted X, …which can deduce the 2 other circular codes in the shifted frames by permutation, is the information used for analysing frameshift genes, i.e. genes with a change of reading frame during translation. This work studies the circular code signal around their frameshift sites. Two scoring methods are developed, a function P based on this code X and a function Q based both on this code X and the 4 trinucleotides with identical nucleotides. They detect a significant correlation between the code X and the −1 frameshift signals in both eukaryotic and prokaryotic genes, and the +1 frameshift signals in eukaryotic genes. Show more

Keywords: Frameshift gene, frameshift signal, circular code, trinucleotide, frame, statistical method

Citation: In Silico Biology, vol. 7, no. 2, pp. 155-168, 2007

Authors: Ranganath, Aruna | Shet, K. Chandra Shekar | Vidyavathi, Nagardone

Article Type: Research Article

Abstract: Structural Genomics initiatives are generating an increasing number of protein structures with very limited biochemical characterization. Characterization of a protein's function and understanding the specific nature of a protein's binding is a critical part of both protein engineering and structure-based drug discovery. The accurate detection of binding site in these protein structures can be valuable in determining its function. As shape plays a crucial role in bimolecular recognition and function, the development of …shape analysis techniques is important for understanding protein structure-function relationships. This paper describes the use of the continuous wavelet transforms (CWT) for characterizing shape features of 3D protein structures. The goal is to explore the CWT as a multiscale tool to generate rotation- and translation-invariant shape features. Show more

Keywords: Continuous wavelet transforms, shape analysis

Citation: In Silico Biology, vol. 7, no. 2, pp. 169-174, 2007

Authors: Mondal, Sukanta | Babu, Rajasekaran Mohan | Bhavna, Rajasekaran | Ramakumar, Suryanarayanarao

Article Type: Research Article

Abstract: A novel conotoxin pl14a containing 25 amino acid residues with an amidated C-terminus from vermivorous cone snail, Conus planorbis belongs to J-conotoxin superfamily and this is the first conotoxin, which inhibits both nicotinic acetylcholine receptor subtypes and Kv1.6 channel. We have attempted through bioinformatics approaches to elucidate the extent of specificity of pl14a towards Kv1 channel subtypes (Kv1.1-Kv1.6). Our work provides rationale for the relatively high specificity and binding mode of pl14a to Kv1.6 …channel.The pl14a peptide contains two types of structural elements, namely the putative dyad (Lys18 and Tyr19) and basic residue ring constituted of arginine residues. We have carried out in silico docking studies so as to assess the contribution of one or combination of both structural elements of pl14a in blocking of Kv1.6 channel. For this purpose, we have built by homology modelling, the theoretical 3D structure of Kv1.6 channel based on the available crystal structure of mammalian shaker Kv1.2 channel. Docking studies suggest that positively charged residues ring may be involved in the blocking mechanism of Kv1.6 channel. The models suggest that the peptide interacts with negatively charged extracellular loops and pore-mouth of the potassium channel and blocks the channel by covering the pore as a lid, akin to previously proposed blocking mechanism of κM-conotoxin RIIIK from Conus radiatus to Tsha1 potassium channel. The newly detected pharmacophore for pl14a interacting with Kv1.6 channel provides a pointer to experimental work to validate the observations made here. Based on differences in the number and distribution of the positively-charged residues in other conopeptides from the J-superfamily, we hypothesize different selectivity profiles against subtypes of the potassium channels for these conopeptides. Show more

Keywords: Conotoxin superfamily, Kv1 channel inhibitor, functional dyad, basic residues ring, pore-loop region, homology modelling, docking

Citation: In Silico Biology, vol. 7, no. 2, pp. 175-186, 2007

Authors: Srinivasan, Bharath | Balaram, Hemalatha

Article Type: Research Article

Abstract: cN-II class of 5' purine nucleotidases exhibit specificity for IMP/GMP and belong to the HAD (haloacid dehalogenase) superfamily of hydrolases. The recently identified ISN1 class of IMP specific 5'-nucleotidases occurring in yeast, fungi and certain Plasmodia lack sequence homology with the cN-II class of enzymes. We show from analysis of motif and fold conservation that ISN1s also belong to the HAD superfamily. This identification adds a new novel member to this superfamily.

Keywords: Purine nucleotidase, ISN1 nucleotidase, HAD superfamily, distant homology modeling, phylogenetic analysis

Citation: In Silico Biology, vol. 7, no. 2, pp. 187-193, 2007

Authors: Yao, Jiqiang | Lin, Hong | Doddapaneni, Harshavardhan | Civerolo, Edwin L.

Article Type: Research Article

Abstract: The increasing number of whole genomic sequences of microorganisms has led to the complexity of genome-wide annotation and gene sequence comparison among multiple microorganisms. To address this problem, we have developed nWayComp software that compares DNA and protein sequences of phylogenetically-related microorganisms. This package integrates a series of bioinformatics tools such as BLAST, ClustalW, ALIGN, PHYLIP and PRIMER3 for sequence comparison. It searches for homologous sequences among multiple organisms and identifies genes …that are unique to a particular organism. The homologous gene sets are then ranked in the descending order of the sequence similarity. For each set of homologous sequences, a table of sequence identity among homologous genes along with sequence variations such as SNPs and INDELS is developed, and a phylogenetic tree is constructed. In addition, a common set of primers that can amplify all the homologous sequences are generated. The nWayComp package provides users with a quick and convenient tool to compare genomic sequences among multiple organisms at the whole-genome level. Show more

Keywords: Sequence comparison, homology, unique, SNP, INDEL, Phylip, primer

Citation: In Silico Biology, vol. 7, no. 2, pp. 195-200, 2007

Authors: Grover, Atul | Sharma, Prakash C.

Article Type: Research Article

Abstract: Microsatellites, arrays of 1–6 bp sequences, are abundant in almost all the eukaryotic genomes. Their distribution in the genome is widely accepted to be differential and non random along the axis of the chromosomes. Arabidopsis thaliana genome is dominated by mononucleotide repeats, (A)_{n} being the most abundant motif. In total, 39 microsatellite motifs extended to more than 100 bp in length. Of these, 8 loci are devoid of any gene in their proximity. …(AG)_{n} is the most abundant motif among longer repeats. The non-random distribution of microsatellite in the genome is reflected as occurrence of microsatellite clusters in the genome. In total, 3400 microsatellite clusters have been identified in the Arabidopsis genome. Chromosome 2, which is 19.7 Mb long, harbors 550 clusters accommodating 29% of all the microsatellites present on this chromosome. Further, 409 of the 6239 genes on chromosome 2 are associated with 323 microsatellite clusters. Motifs like (AGG)_{n} and (ACT)_{n} , show preferential accommodation in clusters that overlap with genes. Among all the microsatellite clusters that show an overlap with genes, 80% of the clusters show an overlap in such a way that the cluster ends beyond the 3'-end of the gene or starts before the 5'-end of a gene. Genes with diverse functions show association with the clusters. However, not all members of a gene family show similar associations. Show more

Keywords: microsatellites, SSRs, microsatellite clustering, Arabidopsis thaliana

Citation: In Silico Biology, vol. 7, no. 2, pp. 201-213, 2007