Effect of DNA structural flexibility on promoter strength—molecular dynamics studies of E. coli promoter sequences

2006 ◽  
Vol 341 (2) ◽  
pp. 557-566
Author(s):  
S. Thiyagarajan ◽  
S.S. Rajan ◽  
N. Gautham
Keyword(s):  
Molecular Dynamics ◽  
Structural Flexibility ◽  
Promoter Strength ◽  
Promoter Sequences ◽  
E Coli ◽  
Coli Promoter

BIOLOGICAL DATA MINING USING BAYESIAN NEURAL NETWORKS: A CASE STUDY

1999 ◽  
Vol 08 (04) ◽  
pp. 433-451 ◽  
Author(s):  
QICHENG MA ◽  
JASON T. L. WANG
Keyword(s):  
Data Mining ◽  
Neural Networks ◽  
Biological Data ◽  
Ensemble Of Classifiers ◽  
Significant Information ◽  
Bayesian Neural Networks ◽  
Promoter Sequences ◽  
E Coli ◽  
Coli Promoter

Biological data mining is the activity of finding significant information in biomolecular data. The significant information may refer to motifs, clusters, genes, and protein signatures. This paper presents an example of biological data mining: the recognition of promoters in DNA. We propose a two-level ensemble of classifiers to recognize E. Coli promoter sequences. The first-level classifiers include three Bayesian neural networks that learn from three different feature sets. The outputs of the first-level classifiers are combined in the second-level to give the final result. Empirical study shows that a precision rate of 92.2% is achieved, indicating an excellent performance of the proposed approach.

scholarly journals A New Type of Fusion Analysis Applicable to Many Organisms: Protein Fusions to the URA3 Gene of Yeast

Genetics ◽  
1987 ◽  
Vol 117 (1) ◽  
pp. 5-12
Author(s):  
Eric Alani ◽  
Nancy Kleckner
Keyword(s):  
Gene Fusion ◽  
Enzyme Assay ◽  
Decarboxylase Activity ◽  
Lacz Gene ◽  
Coding Region ◽  
Ura3 Gene ◽  
Promoter Sequences ◽  
E Coli ◽  
New Type ◽  
Fusion Analysis

ABSTRACT We have made constructs that join the promoter sequences and a portion of the coding region of the Saccharomyces cerevisiae HIS4 and GAL1 genes and the E. coli lacZ gene to the sixth codon of the S. cerevisiae URA3 gene (encodes orotidine-5′-phosphate (OMP) decarboxylase) to form three in frame protein fusions. In each case the fusion protein has OMP decarboxylase activity as assayed by complementation tests and this activity is properly regulated. A convenient cassette consisting of the URA3 segment plus some immediately proximal amino acids of HIS4C is available for making URA3 fusions to other proteins of interest. URA3 fusions offer several advantages over other systems for gene fusion analysis: the URA3 specified protein is small and cytosolic; genetic selections exist to identify mutants with either increased or decreased URA3 function in both yeast (S. cerevisiae and Schizosaccharomyces pombe) and bacteria (Escherichia coli and Salmonella typhimurium); and a sensitive OMP decarboxylase enzyme assay is available. Also, OMP decarboxylase activity is present in mammals, Drosophila and plants, so URA3 fusions may eventually be applicable in these other organisms as well.

scholarly journals Molecular Dynamics Simulations of the Predicted E. Coli FtsB-FtsL Tetrameric Complex

2017 ◽  
Vol 112 (3) ◽  
pp. 501a
Author(s):  
Gladys Diaz Vazquez ◽  
Samson Condon ◽  
Qiang Cui ◽  
Alessandro Senes
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
E Coli ◽  
Dynamics Simulations ◽  
Tetrameric Complex

scholarly journals Ketoamide Resistance and Hepatitis C Virus Fitness in Val55 Variants of the NS3 Serine Protease

2012 ◽  
Vol 56 (4) ◽  
pp. 1907-1915 ◽  
Author(s):  
Christoph Welsch ◽  
Sabine Schweizer ◽  
Tetsuro Shimakami ◽  
Francisco S. Domingues ◽  
Seungtaek Kim ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Rna Replication ◽  
Viral Fitness ◽  
Dynamics Simulation ◽  
Structural Flexibility ◽  
Residue Interaction

ABSTRACTDrug-resistant viral variants are a major issue in the use of direct-acting antiviral agents in chronic hepatitis C. Ketoamides are potent inhibitors of the NS3 protease, with V55A identified as mutation associated with resistance to boceprevir. Underlying molecular mechanisms are only partially understood. We applied a comprehensive sequence analysis to characterize the natural variability at Val55 within dominant worldwide patient strains. A residue-interaction network and molecular dynamics simulation were applied to identify mechanisms for ketoamide resistance and viral fitness in Val55 variants. An infectious H77S.3 cell culture system was used for variant phenotype characterization. We measured antiviral 50% effective concentration (EC50) and fold changes, as well as RNA replication and infectious virus yields from viral RNAs containing variants. Val55 was found highly conserved throughout all hepatitis C virus (HCV) genotypes. The conservative V55A and V55I variants were identified from HCV genotype 1a strains with no variants in genotype 1b. Topology measures from a residue-interaction network of the protease structure suggest a potential Val55 key role for modulation of molecular changes in the protease ligand-binding site. Molecular dynamics showed variants with constricted binding pockets and a loss of H-bonded interactions upon boceprevir binding to the variant proteases. These effects might explain low-level boceprevir resistance in the V55A variant, as well as the Val55 variant, reduced RNA replication capacity. Higher structural flexibility was found in the wild-type protease, whereas variants showed lower flexibility. Reduced structural flexibility could impact the Val55 variant's ability to adapt for NS3 domain-domain interaction and might explain the virus yield drop observed in variant strains.

scholarly journals Mutational Analysis of the ompA Promoter from Flavobacterium johnsoniae

2007 ◽  
Vol 189 (14) ◽  
pp. 5108-5118 ◽  
Author(s):  
Shicheng Chen ◽  
Michael Bagdasarian ◽  
Michael G. Kaufman ◽  
Adam K. Bates ◽  
Edward D. Walker
Keyword(s):  
Promoter Activity ◽  
Mutational Analysis ◽  
Core Promoter ◽  
Gc Content ◽  
Pronounced Effect ◽  
Promoter Elements ◽  
Spacer Length ◽  
Promoter Sequences ◽  
E Coli ◽  
Flavobacterium Johnsoniae

ABSTRACT Sequences that mediate the initiation of transcription in Flavobacterium species are not well known. The majority of identified Flavobacterium promoter elements show homology to those of other members of the phylum Bacteroidetes, but not of proteobacteria, and they function poorly in Escherichia coli. In order to analyze the Flavobacterium promoter structure systematically, we investigated the −33 consensus element, −7 consensus element, and spacer length of the Flavobacterium ompA promoter by measuring the effects of site-directed mutations on promoter activity. The nonconserved sequences in the spacer region and in regions close to the consensus motifs were randomized in order to determine their importance for promoter activity. Most of the base substitutions in these regions caused large decreases in promoter activity. The optimal −33/−7 motifs (TTTG/TANNTTTG) were identical to Bacteroides fragilis σABfr consensus −33/−7 promoter elements but lacked similarity to the E. coli σ70 promoter elements. The length of the spacer separating the −33 and −7 motifs of the ompA promoter also had a pronounced effect on promoter activity, with 19 bp being optimal. In addition to the consensus promoter elements and spacer length, the GC content of the core promoter sequences had a pronounced effect on Flavobacterium promoter activity. This information was used to conduct a scan of the Flavobacterium johnsoniae and B. fragilis genomes for putative promoters, resulting in 188 hits in B. fragilis and 109 hits in F. johnsoniae.

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