Abstract:
:The accuracy of a homology model based on the structure of a distant relative or other topologically equivalent protein is primarily limited by the quality of the alignment. Here we describe a systematic approach for sequence-to-structure alignment, called 'K*Sync', in which alignments are generated by dynamic programming using a scoring function that combines information on many protein features, including a novel measure of how obligate a sequence region is to the protein fold. By systematically varying the weights on the different features that contribute to the alignment score, we generate very large ensembles of diverse alignments, each optimal under a particular constellation of weights. We investigate a variety of approaches to select the best models from the ensemble, including consensus of the alignments, a hydrophobic burial measure, low- and high-resolution energy functions, and combinations of these evaluation methods. The effect on model quality and selection resulting from loop modeling and backbone optimization is also studied. The performance of the method on a benchmark set is reported and shows the approach to be effective at both generating and selecting accurate alignments. The method serves as the foundation of the homology modeling module in the Robetta server.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Chivian D,Baker Ddoi
10.1093/nar/gkl480subject
Has Abstractpub_date
2006-01-01 00:00:00pages
e112issue
17eissn
0305-1048issn
1362-4962pii
gkl480journal_volume
34pub_type
杂志文章abstract::The contacts of phosphate groups in mRNAs with ribosomes were studied. Two mRNAs were used: one mRNA contained in the middle two defined codons to construct the pre- and the post-translocational states, the other was a sequence around the initiation site of the natural cro-mRNA. Phosphorothioate nucleotides were rando...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.12.2228
更新日期:1996-06-15 00:00:00
abstract::Although Dicer is essential for general microRNA (miRNA) biogenesis, vertebrate mir-451 is Dicer independent. Instead, its short pre-miRNA hairpin is 'sliced' by Ago2, then 3'-resected into mature miRNAs. Here, we show that Drosophila cells and animals generate functional small RNAs from mir-451-type precursors. Howev...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1038
更新日期:2014-02-01 00:00:00
abstract::Multiple myeloma, the second most frequent hematologic tumor after lymphomas, is an incurable cancer. Recent sequencing efforts have identified the ribonuclease DIS3 as one of the most frequently mutated genes in this disease. DIS3 represents the catalytic subunit of the exosome, a macromolecular complex central to th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv387
更新日期:2015-05-26 00:00:00
abstract::Ribosome biogenesis is a key process for maintaining protein synthetic capacity in dividing or growing cells, and requires coordinated production of ribosomal proteins and ribosomal RNA (rRNA), including the processing of the latter. Signalling through mammalian target of rapamycin complex 1 (mTORC1) activates all the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku130
更新日期:2014-04-01 00:00:00
abstract::Ribonucleoprotein (RNP) granules are membraneless organelles (MLOs), which majorly consist of RNA and RNA-binding proteins and are formed via liquid-liquid phase separation (LLPS). Experimental studies investigating the drivers of LLPS have shown that intrinsically disordered proteins (IDPs) and nucleic acids like RNA...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa1099
更新日期:2020-12-16 00:00:00
abstract::Cell cycle checkpoints induced by DNA damage play an integral role in preservation of genomic stability by allowing cells to limit the propagation of deleterious mutations. The retinoblastoma tumor suppressor (RB) is crucial for the maintenance of the DNA damage checkpoint function because it elicits cell cycle arrest...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg919
更新日期:2004-01-02 00:00:00
abstract::We describe a new, broadly applicable methodology for screening in parallel interactions of RNA-binding proteins (RBPs) with large numbers of microRNA (miRNA) precursors and for determining their affinities in native form in the presence of cellular factors. The assays aim at identifying pre-miRNAs that are potentiall...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1197
更新日期:2013-02-01 00:00:00
abstract::Differential scanning microcalorimetry (DSC), UV absorption and circular dichroism (CD) have been used to study structure and stability of linear (lin), open circular (oc), supercoiled (cd) and relaxed circular duplex (rd) DNA and calf thymus (CT) DNA. Investigations were made in low salt buffer and in the presence of...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.24.11737
更新日期:1988-12-23 00:00:00
abstract::Polymers of random 14 mer oligonucleotides are shown to detect discrete loci in the human genome. Eighteen different synthetic tandem repeats of random 14 base-pair units (STRs) have been generated and all of them turn out to detect polymorphic loci on southern blots of human DNA samples, presumably corresponding to a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.19.7623
更新日期:1989-10-11 00:00:00
abstract::The Functional Single Nucleotide Polymorphism (F-SNP) database integrates information obtained from 16 bioinformatics tools and databases about the functional effects of SNPs. These effects are predicted and indicated at the splicing, transcriptional, translational and post-translational level. As such, the database h...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm904
更新日期:2008-01-01 00:00:00
abstract::The thermal stabilities of RNA:DNA hybrids are substantially greater than those of DNA:DNA duplexes in aqueous electrolyte solutions containing high concentrations of formamide. Association rates to form DNA:DNA duplexes and DNA:RNA hybrids have been measured in these solvents. There is a temperature range in which DN...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.5.1539
更新日期:1977-01-01 00:00:00
abstract::The NusA protein is a universally conserved bacterial transcription elongation factor that binds RNA polymerase (RNAP). When functioning independently, NusA enhances intrinsic termination. Paradoxically, NusA stimulates the function of the N and Q antiterminator proteins of bacteriophage λ. The mechanistic basis for N...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw198
更新日期:2016-06-20 00:00:00
abstract::Variable (diversity) joining [V(D)J] recombination of immune gene loci proceeds in an ordered manner with D to J portions recombining first and then an upstream V joins that recombinant. We present evidence that the non-core domain of recombination activating gene (RAG) protein 2 is involved in the regulation of recom...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn553
更新日期:2008-10-01 00:00:00
abstract::A crucial component of the human mitochondrial DNA replisome is the ring-shaped helicase TWINKLE-a phage T7-gene 4-like protein expressed in the nucleus and localized in the human mitochondria. Our previous studies showed that despite being a helicase, TWINKLE has unique DNA annealing activity. At the time, the implic...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw098
更新日期:2016-05-19 00:00:00
abstract::Exposure to genotoxic agents, such as ionizing radiation (IR), produces double-strand breaks, repaired predominantly in mammalian cells by non-homologous end-joining (NHEJ). Ku70 was identified as an interacting partner of a proteolytic Cyclin E (CycE) fragment, p18CycE. p18CycE endogenous generation during IR-induced...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt812
更新日期:2013-12-01 00:00:00
abstract::In Saccharomyces cerevisiae, the DNA damage response (DDR) is activated by the spatio-temporal colocalization of Mec1-Ddc2 kinase and the 9-1-1 clamp. In the absence of direct means to monitor Mec1 kinase activation in vivo, activation of the checkpoint kinase Rad53 has been taken as a proxy for DDR activation. Here, ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp1222
更新日期:2010-04-01 00:00:00
abstract::Members of the basic helix-loop-helix (bHLH) family of transcription factors regulate a wide array of developmental processes in many cell types, including cell fate specification, differentiation and morphogenesis. Our studies describe the cloning of a gene from the nematode Caenorhabditis elegans that is closely rel...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.21.4423
更新日期:2001-11-01 00:00:00
abstract::To investigate the principles driving recognition between proteins and DNA, we analyzed more than thousand crystal structures of protein/DNA complexes. We classified protein and DNA conformations by structural alphabets, protein blocks [de Brevern, Etchebest and Hazout (2000) (Bayesian probabilistic approach for predi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1273
更新日期:2014-03-01 00:00:00
abstract::A novel, site-specific, DNA backbone S-modification (phosphorothioation) has been discovered, but its in vivo function(s) have remained obscure. Here, we report that the enteropathogenic Salmonella enterica serovar Cerro 87, which possesses S-modified DNA, restricts DNA isolated from Escherichia coli, while protecting...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq610
更新日期:2010-11-01 00:00:00
abstract::Many DNA modification and repair enzymes require access to DNA bases and therefore flip nucleotides. Restriction endonucleases (REases) hydrolyze the phosphodiester backbone within or in the vicinity of the target recognition site and do not require base extrusion for the sequence readout and catalysis. Therefore, the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm513
更新日期:2007-01-01 00:00:00
abstract::HotSpot Wizard is a web server used for the automated identification of hotspots in semi-rational protein design to give improved protein stability, catalytic activity, substrate specificity and enantioselectivity. Since there are three orders of magnitude fewer protein structures than sequences in bioinformatic datab...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky417
更新日期:2018-07-02 00:00:00
abstract::Synchronized cells of a normal human lymphocytic cell line contain little swiven enzyme activity in G0 and G1 and high activity in Sphase. The level of activity in different growth phase appears to be related to the fraction of the population engaged in DNA replication. No endogenous inhibitor or activator of swiven a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/3.12.3305
更新日期:1976-12-01 00:00:00
abstract::Protein p56 (56 amino acids) from the Bacillus subtilis phage 29 inactivates the host uracil-DNA glycosylase (UDG), an enzyme involved in the base excision repair pathway. At present, p56 is the only known example of a UDG inhibitor encoded by a non-uracil containing viral DNA. Using analytical ultracentrifugation met...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm584
更新日期:2007-01-01 00:00:00
abstract::A number of different protecting groups were compared with respect to their usefulness for protection of 2'-hydroxyl functions during synthesis of oligoribonucleotides using the H-phosphonate approach. The comparison was between the t-butyldimethylsilyl (t-BDMSi), the o-chlorobenzoyl (o-CIBz), the tetrahydropyranyl (T...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.1.94
更新日期:1994-01-11 00:00:00
abstract::Highly repetitive Hind III restriction fragments of 0.72-0.76 KBP from total Xenopus laevis genomic DNA are organized in a tandem like arrangement. Cloning of these fragments in pBR 322 with subsequent restriction site mapping and nucleotide sequence analysis of some selected clones showed two different types of seque...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.20.6997
更新日期:1983-10-25 00:00:00
abstract::The pol gene of all retroviruses is expressed as a gag-pol fusion protein which is proteolytically processed to produce all viral enzymes. In the human immunodeficiency virus (HIV), the gag and pol genes overlap by 241 nucleotides with pol in the -1 phase with respect to gag. The gag-pol fusion is produced via a -1 ri...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.15.3945
更新日期:1992-08-11 00:00:00
abstract::To generate long arrays of nucleosomes within a topologically defined chromatin domain we have assembled minichromosomes on negatively supercoiled plasmid DNA with extracts from Drosophila preblastoderm embryos. These minichromosomes are dynamic substrates for energy-dependent nucleosome remodeling machines that facil...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.16.3657
更新日期:1998-08-15 00:00:00
abstract::The RNA bacteriophages of E. coli specifically encapsidate a single copy of the viral genome in a protein shell composed mainly of 180 molecules of coat protein. Coat protein is also a translational repressor and shuts off viral replicase synthesis by interaction with a RNA stem-loop containing the replicase initiatio...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.19.4621
更新日期:1993-09-25 00:00:00
abstract::Bgee is a database to retrieve and compare gene expression patterns in multiple animal species, produced by integrating multiple data types (RNA-Seq, Affymetrix, in situ hybridization, and EST data). It is based exclusively on curated healthy wild-type expression data (e.g., no gene knock-out, no treatment, no disease...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa793
更新日期:2021-01-08 00:00:00
abstract::Sae2 cooperates with the Mre11-Rad50-Xrs2 (MRX) complex to initiate resection of DNA double-strand breaks (DSBs) and to maintain the DSB ends in close proximity to allow their repair. How these diverse MRX-Sae2 functions contribute to DNA damage resistance is not known. Here, we describe mre11 alleles that suppress th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky086
更新日期:2018-04-06 00:00:00