Abstract:
:Molecular models of six anthracycline antibiotics and their complexes with 32 distinct DNA octamer sequences were created and analyzed using HINT (Hydropathic INTeractions) to describe binding. The averaged binding scores were then used to calculate the free energies of binding for comparison with experimentally determined values. In parsing our results based on specific functional groups of doxorubicin, our calculations predict a free energy contribution of -3.6 +/- 1.1 kcal x mol(-1) (experimental -2.5 +/- 0.5 kcal x mol(-1)) from the groove binding daunosamine sugar. The net energetic contribution of removing the hydroxyl at position C9 is -0.7 +/- 0.7 kcal x mol(-1) (-1.1 +/- 0.5 kcal x mol(-1)). The energetic contribution of the 3' amino group in the daunosamine sugar (when replaced with a hydroxyl group) is -3.7 +/- 1.1 kcal x mol(-1) (-0.7 +/- 0.5 kcal x mol(-1)). We propose that this large discrepancy may be due to uncertainty in the exact protonation state of the amine. The energetic contribution of the hydroxyl group at C14 is +0.4 +/- 0.6 kcal x mol(-1) (-0.9 +/- 0.5 kcal x mol(-1)), largely due to unfavorable hydrophobic interactions between the hydroxyl oxygen and the methylene groups of the phosphate backbone of the DNA. Also, there appears to be considerable conformational uncertainty in this region. This computational procedure calibrates our methodology for future analyses where experimental data are unavailable.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Cashman DJ,Scarsdale JN,Kellogg GEdoi
10.1093/nar/gkg645keywords:
subject
Has Abstractpub_date
2003-08-01 00:00:00pages
4410-6issue
15eissn
0305-1048issn
1362-4962journal_volume
31pub_type
杂志文章abstract::In order to systematically analyze the effects of nucleoside modification of sugar moieties in DNA polymerase reactions, we synthesized 16 modified templates containing 2',4'-bridged nucleotides and three types of 2',4'-bridged nucleoside-5'-triphospates with different bridging structures. Among the five types of ther...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn404
更新日期:2008-08-01 00:00:00
abstract::Adenosine deaminases that act on RNA (ADARs) convert adenosine to inosine within double-stranded regions of RNA, resulting in increased transcriptomic diversity, as well as protection of cellular double-stranded RNA (dsRNA) from silencing and improper immune activation. The presence of dsRNA-binding domains (dsRBDs) i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky800
更新日期:2018-10-12 00:00:00
abstract::Nucleotide sequences of three cloned restriction fragments of Tetrahymena mtDNA which showed hybridization with mitochondrial tRNA have been determined. EcoRI fragment 5 (4.1 kbp) contains the tRNAphe gene sequence with anticodon GAA; Hind III fragment 6 (2.0 kbp) the tRNAhis with anticodon GTG; and EcoRI fragment 7 (...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.9.3273
更新日期:1985-05-10 00:00:00
abstract::Naturally occurring RNAs are known to exhibit a high degree of modularity, whereby specific structural modules (or motifs) can be mixed and matched to create new molecular architectures. The modular nature of RNA also affords researchers the ability to characterize individual structural elements in controlled syntheti...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz304
更新日期:2019-07-09 00:00:00
abstract::Recent rapid advances in next generation RNA sequencing (RNA-Seq)-based provide researchers with unprecedentedly large data sets and open new perspectives in transcriptomics. Furthermore, RNA-Seq-based transcript profiling can be applied to non-model and newly discovered organisms because it does not require a predefi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks540
更新日期:2012-07-01 00:00:00
abstract::We describe the synthesis of 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides and demonstrate their utility as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. These 2'-O-modified compounds were designed to possess the binding affinity of an RNA molecule t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.10.2629
更新日期:1991-05-25 00:00:00
abstract::Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx693
更新日期:2017-09-19 00:00:00
abstract::POGO-DB (http://pogo.ece.drexel.edu/) provides an easy platform for comparative microbial genomics. POGO-DB allows users to compare genomes using pre-computed metrics that were derived from extensive computationally intensive BLAST comparisons of >2000 microbes. These metrics include (i) average protein sequence ident...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1094
更新日期:2014-01-01 00:00:00
abstract::Retroviral particles contain a dimeric RNA genome, which serves as template for the generation of double-stranded DNA by reverse transcription. Transfer between RNA strands during DNA synthesis is governed by both sequence similarity between templates and structural features of the dimeric RNA. A kissing hairpin, beli...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh159
更新日期:2004-01-09 00:00:00
abstract::The bacterial transcription terminator, Rho, terminates transcription at half of the operons. According to the classical model derived from in vitro assays on a few terminators, Rho is recruited to the transcription elongation complex (EC) by recognizing specific sites (rut) on the nascent RNA. Here, we explored the m...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku690
更新日期:2014-09-01 00:00:00
abstract::We have examined the interactions of UvrABC endonuclease with DNA containing the monoadducts of 8-methoxypsoralen (8-MOP) and 4,5',8-trimethylpsoralen (TMP). The UvrA and UvrB proteins were found to form a stable complex on DNA that contains the psoralen monoadducts. Subsequent binding of UvrC protein to this complex ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.12.4957
更新日期:1987-06-25 00:00:00
abstract::The base pairing properties of oligonucleotide duplexes containing 8-aza-7-deaza-2'-deoxyisoguanosine, its 7-bromo or its 7-iodo derivative are described. The nucleosides were synthesized on a convergent route, protected and converted into phosphoramidites. Oligonucleotides were prepared on a solid-phase and were hybr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg926
更新日期:2003-12-15 00:00:00
abstract::The aminoacylation kinetics of T7 transcripts representing defined regions of Escherichia coli serine tRNAs were determined using purified E.coli seryl-tRNA synthetase (SerRS) and the kinetic values were used to estimate the relative contribution of various tRNA(Ser) domains to recognition by SerRS. The analysis revea...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.19.4467
更新日期:1993-09-25 00:00:00
abstract::Human apolipoprotein (apo) B mRNA is edited in a tissue specific reaction, to convert glutamine codon 2153 (CAA) to a stop translation codon. The RNA editing product templates and hybridises as uridine, but the chemical nature of this reaction and the physical identity of the product are unknown. After editing in vitr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.6.1197
更新日期:1991-03-25 00:00:00
abstract::The lambdagt clones containing fragments of the Drosophila melanogaster genome were prepared and characterized by hybridization of their DNA with (I) lambdagt-cRNA; (2) lambdaC-cRNA; (3) Dm-cRNA; (4) the mRNA of D.melanogaster culture cells and (5) the stable cytoplasmic poly (A) RNA from the same source. The techniqu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/3.8.2115
更新日期:1976-08-01 00:00:00
abstract::We have developed a comprehensive resource devoted to biologists wanting to optimize the use of gene trap clones in their experiments. We have processed 300 602 such clones from both public and private projects to generate 28,199 'UniTraps', i.e. distinct collections of unambiguous insertions at the same subgenic regi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm825
更新日期:2008-01-01 00:00:00
abstract::RNA molecules play different roles in coding, decoding and gene expression regulation. Such roles are often associated to the RNA secondary or tertiary structures. The folding dynamics lead to multiple secondary structures of long RNA molecules, since an RNA molecule might fold into multiple distinct native states. De...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku1249
更新日期:2014-12-16 00:00:00
abstract::About 40% of the genes in the nematode Caenorhabditis elegans have homologs in humans. Based on the history of this model system, it is clear that the application of genetic methods to the study of this set of genes would provide important clues to their function in humans. To facilitate such genetic studies, we are e...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gnf051
更新日期:2002-06-15 00:00:00
abstract::Recognizing the methylation status of specific DNA sequences is central to the function of many systems in eukaryotes and prokaryotes. Restriction-modification systems have to distinguish between 'self' and 'non-self' DNA and depend on the inability of restriction endonucleases to cleave their DNA substrates when the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.16.3143
更新日期:2000-08-15 00:00:00
abstract::The Intronerator (http://www.cse.ucsc.edu/ approximately kent/intronerator/ ) is a set of web-based tools for exploring RNA splicing and gene structure in Caenorhabditis elegans. It includes a display of cDNA alignments with the genomic sequence, a catalog of alternatively spliced genes and a database of introns. The ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.1.91
更新日期:2000-01-01 00:00:00
abstract::Furvina®, also denominated G1 (MW 297), is a synthetic nitrovinylfuran [2-bromo-5-(2-bromo-2-nitrovinyl)-furan] antibiotic with a broad antimicrobial spectrum. An ointment (Dermofural®) containing G1 as the only active principle is currently marketed in Cuba and successfully used to treat dermatological infections. He...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks822
更新日期:2012-11-01 00:00:00
abstract::Riboswitches are important gene regulatory elements frequently encountered in bacterial mRNAs. The recently discovered nadA riboswitch contains two similar, tandemly arrayed aptamer domains, with the first domain possessing high affinity for nicotinamide adenine dinucleotide (NAD+). The second domain which comprises t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa1029
更新日期:2020-12-02 00:00:00
abstract::Aberration within the p53 tumor suppressor gene is the most frequently identified genetic damage in human cancer. Regulatory functions proposed for the p53 protein include modulation of the cell cycle, cellular differentiation, signal transduction, and gene expression. Additionally, the p53 gene product may guard the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.3.713
更新日期:1993-02-11 00:00:00
abstract::Selected groups of isolated 14C-labelled proteins from E. coli 30S ribosomal subunits were reconstituted with 32P-labelled 16S RNA, and the reconstituted complexes were partially digested with ribonuclease A. RNA fragments protected by the proteins were separated by gel electrophoresis and subjected to sequence analys...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.4.1233
更新日期:1988-02-25 00:00:00
abstract::HORMA domain-containing proteins (HORMADs) play an essential role in meiosis in many organisms. The meiotic HORMADs, including yeast Hop1, mouse HORMAD1 and HORMAD2, and Arabidopsis ASY1, assemble along chromosomes at early prophase and the closure motif at their C-termini has been hypothesized to be instrumental for ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa527
更新日期:2020-11-18 00:00:00
abstract::We have examined the behaviour of the beta-interferon promoter in mouse F9 embryonal carcinoma cells. In undifferentiated cells, the beta-interferon promoter is not responsive to dsRNA or to Sendai virus. In cells stimulated to differentiate into parietal endoderm by treatment with retinoic acid, the beta-interferon p...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.21.4489
更新日期:1994-10-25 00:00:00
abstract::We have previously reported the isolation of mammalian cell lines expressing the 3-methyladenine DNA glycosylase I (tag) gene from E. coli. These cells are 2-5 fold more resistant to the toxic effects of methylating agents than normal cells (15). Kinetic measurements of 3-methyladenine removal from the genome in situ ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.9.1670
更新日期:1994-05-11 00:00:00
abstract::The accurate structural modeling of B- and T-cell receptors is fundamental to gain a detailed insight in the mechanisms underlying immunity and in developing new drugs and therapies. The LYRA (LYmphocyte Receptor Automated modeling) web server (http://www.cbs.dtu.dk/services/LYRA/) implements a complete and automated ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv535
更新日期:2015-07-01 00:00:00
abstract::The conserved bacterial anticodon nuclease (ACNase) RloC and its phage-excluding homolog PrrC comprise respective ABC-adenosine triphosphatase (ATPase) and ACNase N- and C-domains but differ in three key attributes. First, prrC is always linked to an ACNase silencing, DNA restriction-modification (R-M) locus while rlo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks593
更新日期:2012-09-01 00:00:00
abstract::The current version of PLMItRNA has been realized to constitute a database for tRNA molecules and genes identified in the mitochondria of all green plants ( Viridiplantae ). It is the enlargement of a previous database originally restricted to seed plants [Ceci,L.R., Volpicella,M., Liuni,S., Volpetti,V., Licciulli,F. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.1.159
更新日期:2000-01-01 00:00:00