In Silico Biology - Volume 1, issue 2

Authors: Aravind, L.

Article Type: Research Article

Abstract: All the detectable metallo-â-lactamase fold proteins were identified in the publicly available sequence databases and complete genome sequences using iterative profile searches with the PSI-BLAST program and motif searches with position specific weight matrices. The catalytic site/mechanism and the corresponding structural elements were characterized for these proteins based on the available structure of the Bacillus zinc-dependent â-lactamase. Based on pair-wise sequence and phylogenetic analysis an evolutionary classification for enzymes of this fold …was developed and discussed in terms of implications for substrate specificity. Finally, some predicted inactive members which have been recruited for non-enzymatic functions such as microtubule binding in a cytoskeletal MAP1 are described. Show more

Keywords: ß-lactamase, metal dependent hydrolases, poly-A specific RNA processing, DNA repair, inactive enzymes

Citation: In Silico Biology, vol. 1, no. 2, pp. 69-91, 1999

Authors: Overbeek, Ross | Fonstein, Michael | D'Souza, Mark | Pusch, Gordon D. | Maltsev, Natalia

Article Type: Research Article

Abstract: The availability of a growing number of completely sequenced genomes opens new opportunities for understanding of complex biological systems. Success of genome-based biology will, to a large extent, depend on the development of new approaches and tools for efficient comparative analysis of the genomes and their organization. We have developed a technique for detecting possible functional coupling between genes based on detection of potential operons. The approach involves computation of "pairs of close bidirectional …best hits", which are pairs of genes that apparently occur within operons in multiple genomes. Using these pairs, one can compose evidence (based on the number of distinct genomes and the phylogenetic distance between the orthologous pairs) that a pair of genes is potentially functionally coupled. The technique has revealed a surprisingly rich and apparently accurate set of functionally coupled genes. The approach depends on the use of a relatively large number of genomes, and the amount of detected coupling grows dramatically as the number of genomes increases. Show more

Keywords: microbial genomes, operons, gene function identification, genetic sequence analysis, comparative analysis

Citation: In Silico Biology, vol. 1, no. 2, pp. 93-108, 1999

Authors: Brusic, Vladimir | van Endert, Peter | Zeleznikow, John | Daniel, Soizic | Hammer, Jürgen | Petrovsky, Nikolai

Article Type: Research Article

Abstract: We used an artificial neural network (ANN) computer model to study peptide binding to the human transporter associated with antigen processing (TAP). After validation, an ANN model of TAP-peptide binding was used to mine a database of HLA-binding peptides to elucidate patterns of TAP binding. The affinity of HLA-binding peptides for TAP was found to differ according to the HLA supertype concerned: HLA-B27, -A3 or -A24 binding peptides had high, whereas HLA-A2, -B7 or -B8 binding …peptides had low affinity for TAP. These results support the idea that TAP and particular HLA molecules may have co-evolved for efficient peptide processing and presentation. The strong similarity between the sets of peptides bound by TAP or HLA-B27 suggests functional co-evolution whereas the lack of a relationship between the sets of peptides bound by TAP or HLA-A2 is against these particular molecules having co-evolved. In support of these conclusions, the affinities of HLA-A2 and HLA-B7 binding peptides for TAP show similar distributions to that of randomly generated peptides. On the basis of these results we propose that HLA alleles constitute two separate classes: those that are TAP-efficient for peptide loading (HLA-B27, -A3 and -A24) and those that are TAP-inefficient (HLA-A2, -B7 and -B8). Computer modelling can be used to complement laboratory experiments and thereby speed up knowledge discovery in biology. In particular, we provide evidence that large-scale experiments can be avoided by combining initial experimental data with limited laboratory experiments sufficient to develop and validate appropriate computer models. These models can then be used to perform large-scale simulated experiments the results of which can then be validated by further small-scale laboratory experiments Show more

Keywords: binding, data mining, MHCPEP, HLA, KDD, knowledge discovery from databases, major histocompatibility complex, MHC, peptide, prediction, simulated experiments, transport, translocation,

Citation: In Silico Biology, vol. 1, no. 2, pp. 109-121, 1999

Authors: Prigent, Claude | Gill, Rob | Trower, Mike | Sanseau, Philippe

Article Type: Research Article

Abstract: In this short communication we report for the first time to our knowledge the use of ESTBlast to in silico clone a new gene and a step by step description of this particular in silico cloning project.

Keywords: data mining, ESTs, in silico analysis, BLAST, protein kinase

Citation: In Silico Biology, vol. 1, no. 2, pp. 123-128, 1999