In Silico Biology - Volume 6, issue 4

Authors: Massey, Steven E.

Article Type: Research Article

Abstract: Three aminoacyl-tRNA synthetases from yeast, one from plants and one from mammals possess unusual structures at their N termini, namely α helices with basic residues distributed asymmetrically, on a single face of the helix. It is unknown if these 'basic faced' α helices (BFAHs) are unique to the aminoacyl-tRNA synthetases. Analysis of the amino acid sequences of these five aminoacyl-tRNA synthetases using the hydrophobic moment algorithm failed to accurately identify the BFAHs. A new algorithm was …therefore developed, called the 'basic moment'. This is a Fourier analysis procedure that predicts the distribution of basic residues within protein secondary structure. The basic moment identifies with a high degree of accuracy the five known BFAHs and also identifies further potential BFAHs at evolutionarily conserved positions in the peptide extensions of aspartyl-, lysyl- and valyl- tRNA synthetases from a range of eukaryotic species. In addition, the algorithm identifies the two-helix pair tRNA binding domain of alanyl-tRNA synthetase, implying that the domain includes a BFAH. The functional and evolutionary aspects of these structural features are discussed. Show more

Keywords: Aminoacyl-tRNA synthetase, basic moment, α-helix, hydrophobic moment, Fourier analysis

Citation: In Silico Biology, vol. 6, no. 4, pp. 259-273, 2006

Authors: Sakharkar, Meena Kishore | Kangueane, Pandjassarame | Sakharkar, Kishore Ramaji | Zhong, Zhaowei

Article Type: Research Article

Abstract: Protein lengths vary considerably from a few to thousands of amino acids and length variations are documented to have multiple effects. A computational approach to investigate the functional impact of protein length variation in genetic disorders is presented. The genes for huge proteins are found to have more introns. Our analysis also shows greater involvement of huge proteins in hereditary diseases.

Keywords: Huge proteins, protein length, human, disease, OMIM

Citation: In Silico Biology, vol. 6, no. 4, pp. 275-279, 2006

Authors: Merkl, Rainer

Article Type: Research Article

Abstract: In order to identify and to characterise gene clusters conserved in microbial genomes, the algorithm AMIGOS was developed. It is based on a categorisation of genes using a predefined set of gene functions (GFs). After the categorisation of all genes of a genome and based on their location on a replicon, distances between GFs were determined and stored in genome-specific matrices. These matrices were used to identify GF clusters like those strictly conserved in 13 archaeal, …in 47 bacterial genomes and in the combination of the sets. Within the combined set of these 60 microbial genomes, there exist only two strictly conserved clusters harbouring two ribosomal genes each, namely those for L4, L23 and L22, L29. In order to characterise less strictly conserved GF clusters, content of genomes i.e. matrices were analysed pairwise. Resulting clusters were merged to (meta-) clusters if their content overlapped. A scoring system named cons_{CL} was developed. It quantifies conservedness of cluster membership for individual GFs. For the genome of Escherichia coli it was shown that a grouping of cluster elements on cons_{CL} values dissected the clusters into smaller sets. These sets were frequently overlapped by known transcriptional units (TUs). This finding justifies the usage of cons_{CL} scores to predict TU membership of genes. In addition, cons_{CL} values provide a sound basis for non-homologous gene annotation. Based on cons_{CL} values, examples of conserved clusters containing annotated genes and single ones with unknown function are given. Show more

Keywords: Non-homologous gene annotation, functional coupling, conserved gene clusters, operon prediction

Citation: In Silico Biology, vol. 6, no. 4, pp. 281-306, 2006

Authors: Su, Gang | Mao, Binchen | Wang, Jin

Article Type: Research Article

Abstract: We have implemented a novel gapped-alignment algorithm to compare Position Frequency Matrices (PFMs) for Transcription Factor Binding Sites. The application compares an input PFM with those collected from public databases and outputs similarity scores, sequence alignments and related PFM clusters. MACO is freely accessible on a web server located at www.nicemice.cn/bioinfo/MACO. Source code is distributed upon request to the authors.

Keywords: Position Frequency Matrix (PFM), gap, alignment, transcription factor binding site (TFBS)

Citation: In Silico Biology, vol. 6, no. 4, pp. 307-310, 2006

Authors: Chakrabarti, Saikat | Manohari, Gowri | Pugalenthi, Ganesan | Sowdhamini, Ramanathan

Article Type: Research Article

Abstract: The presence of sequence homologues and the availability of structural information of proteins enable better understanding of the biological function of a protein family. A majority of entries in protein structural databank are single member superfamilies for which it is hard to derive motifs due to the paucity of structural homologues. Important conserved segments for these superfamilies have been identified and compiled into a database, SSToSS (Sequence Structural Templates of Single member Superfamily). …Conserved regions, recognized by permitted amino acid exchanges, are mapped on the structure and various structural features (solvent accessibility, secondary structure content, hydrogen bonding and residue packing) are examined. These conserved segments with high structural feature content are projected as sequence-structural templates for the particular superfamily member. Interactive three-dimensional displays of the templates in three-dimensional structure (in Chime® and RASMOL) are provided for better understanding and visualization. In SSToSS database, we also provide the application of sequence-structural templates in three different areas: multiple-motif based sequence search, multiple sequence alignment and homology modeling. In each case, the inclusion of the sequence-structural templates can give rise to sensitive and accurate results. This enables the inclusion of singletons to provide added value to the recognition of additional members, comparative modeling and in designing experiments. Show more

Keywords: Conserved regions, motif-based database search, comparative modeling, spatial orientation of motifs, superfamily signatures, distant similarity, protein structure prediction

Citation: In Silico Biology, vol. 6, no. 4, pp. 311-319, 2006

Authors: Blackshields, Gordon | Wallace, Iain M. | Larkin, Mark | Higgins, Desmond G.

Article Type: Research Article

Abstract: The most popular way of comparing the performance of multiple sequence alignment programs is to use empirical testing on sets of test sequences. Several such test sets now exist, each with potential strengths and weaknesses. We apply several different alignment packages to 6 benchmark datasets, and compare their relative performances. HOMSTRAD, a collection of alignments of homologous proteins, is regularly used as a benchmark for sequence alignment though it is not designed as such, and lacks …annotation of reliable regions within the alignment. We introduce this annotation into HOMSTRAD using protein structural superposition. Results on each database show that method performance is dependent on the input sequences. Alignment benchmarks are regularly used in combination to measure performance across a spectrum of alignment problems. Through combining benchmarks, it is possible to detect whether a program has been over-optimised for a single dataset, or alignment problem type. Show more

Keywords: Multiple sequence alignment, benchmark, BAliBASE, HOMSTRAD, IRMbase, OxBench, PREFAB, SABmark, structural superposition, RMSD, over-training, over-alignment

Citation: In Silico Biology, vol. 6, no. 4, pp. 321-339, 2006

Authors: Chong, Chan-Eng | Lim, Boon-San | Nathan, Sheila | Mohamed, Rahmah

Article Type: Research Article

Abstract: Recent advances in DNA sequencing technology have enabled elucidation of whole genome information from a plethora of organisms. In parallel with this technology, various bioinformatics tools have driven the comparative analysis of the genome sequences between species and within isolates. While drawing meaningful conclusions from a large amount of raw material, computer-aided identification of suitable targets for further experimental analysis and characterization, has also led to the prediction of non-human homologous essential …genes in bacteria as promising candidates for novel drug discovery. Here, we present a comparative genomic analysis to identify essential genes in Burkholderia pseudomallei. Our in silico prediction has identified 312 essential genes which could also be potential drug candidates. These genes encode essential proteins to support the survival of B. pseudomallei including outer-inner membrane and surface structures, regulators, proteins involved in pathogenenicity, adaptation, chaperones as well as degradation of small and macromolecules, energy metabolism, information transfer, central/intermediate/miscellaneous metabolism pathways and some conserved hypothetical proteins of unknown function. Therefore, our in silico approach has enabled rapid screening and identification of potential drug targets for further characterization in the laboratory. Show more

Keywords: Burkholderia pseudomallei, minimal gene set, drug targets, essential genes, comparative genome analysis, orthologous target genes, antimicrobial targets

Citation: In Silico Biology, vol. 6, no. 4, pp. 341-346, 2006

Authors: Escobar, Andrés J. Gutiérrez | Arenas, Aylan Farid | Gómez-Marin, Jorge Enrique

Article Type: Research Article

Abstract: The serine-rich (SR) protein family is involved in the pre-mRNA splicing process and the DNA sequences of the corresponding genes are highly conserved in the metazoan organisms. The mammalian SR proteins consist of one or two characteristic RNA binding domains (RBD), containing the signature sequences RDAEDA and SWQDLKD and a RS (arginine/serine-rich) domain. We used the amino acid and nucleotide sequences deposited in GenBank and Swiss-Prot databases to perform a phylogenetic analysis using bioinformatics tools. The …results of the phylogenetic trees suggest that this family has evolved by several gene duplication events as a result of a positive selection mechanism. Show more

Keywords: SR protein family, splicing, Toxoplasma, molecular evolution

Citation: In Silico Biology, vol. 6, no. 4, pp. 347-350, 2006