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1.
Blood ; 135(1): 41-55, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697823

RESUMO

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, in which multiple subclones harbor mutations in the same drug resistance gene, was observed in 6 relapses and confirmed by single-cell sequencing in 1 case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently a 2-step process in which a persistent clone survived initial therapy and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from preexisting resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31853777

RESUMO

A highly efficient lycopene production system was constructed by assembling enzymes fused to zinc-finger motifs on DNA scaffolds in vitro and in vivo. Three key enzymes of the lycopene synthesis pathway, geranylgeranyl diphosphate synthase, phytoene synthase, and phytoene desaturase, were fused with zinc-finger proteins, expressed and purified. Recombinant plasmids of the pS series containing DNA scaffolds that the zinc-finger proteins can specifically bind to were constructed. In the in vitro system, the production efficiency of lycopene was improved greatly after the addition of the scaffold plasmid pS231. Subsequently, the plasmid pET-AEBI was constructed and introduced into recombinant Escherichia coli BL21 (DE3) for expression, together with plasmids of the pS series. The lycopene production rate and content of the recombinant strain pp231 were higher than that of all strains carrying the DNA scaffold and the control. With the addition of cofactors and substrates in the lycopene biosynthesis pathway, the lycopene yield of pp231 reached 632.49 mg/L at 40 h, representing a 4.7-fold increase compared to the original recombinant strain pA1A3. This DNA scaffold system can be used as a platform for the construction and production of many biochemicals synthesized via multi-enzyme cascade reactions.

3.
Nat Commun ; 10(1): 2789, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243274

RESUMO

IGH@ proto-oncogene translocation is a common oncogenic event in lymphoid lineage cancers such as B-ALL, lymphoma and multiple myeloma. Here, to investigate the interplay between IGH@ proto-oncogene translocation and IGH allelic exclusion, we perform long-read whole-genome and transcriptome sequencing along with epigenetic and 3D genome profiling of Nalm6, an IGH-DUX4 positive B-ALL cell line. We detect significant allelic imbalance on the wild-type over the IGH-DUX4 haplotype in expression and epigenetic data, showing IGH-DUX4 translocation occurs on the silenced IGH allele. In vitro, this reduces the oncogenic stress of DUX4 high-level expression. Moreover, patient samples of IGH-DUX4 B-ALL have similar expression profile and IGH breakpoints as Nalm6, suggesting a common mechanism to allow optimal dosage of non-toxic DUX4 expression.


Assuntos
Proteínas de Homeodomínio/metabolismo , Cadeias Pesadas de Imunoglobulinas/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Animais , Apoptose , DNA/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Genômica , Histonas , Humanos , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Sequenciamento Completo do Genoma
4.
Nucleic Acids Res ; 47(13): 6699-6713, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31127282

RESUMO

Numerous pieces of evidence support the complex, 3D spatial organization of the genome dictates gene expression. CTCF is essential to define topologically associated domain boundaries and to facilitate the formation of insulated chromatin loop structures. To understand CTCF's direct role in global transcriptional regulation, we integrated the miniAID-mClover3 cassette to the endogenous CTCF locus in a human pediatric B-ALL cell line, SEM, and an immortal erythroid precursor cell line, HUDEP-2, to allow for acute depletion of CTCF protein by the auxin-inducible degron system. In SEM cells, CTCF loss notably disrupted intra-TAD loops and TAD integrity in concurrence with a reduction in CTCF-binding affinity, while showing no perturbation to nuclear compartment integrity. Strikingly, the overall effect of CTCF's loss on transcription was minimal. Whole transcriptome analysis showed hundreds of genes differentially expressed in CTCF-depleted cells, among which MYC and a number of MYC target genes were specifically downregulated. Mechanically, acute depletion of CTCF disrupted the direct interaction between the MYC promoter and its distal enhancer cluster residing ∼1.8 Mb downstream. Notably, MYC expression was not profoundly affected upon CTCF loss in HUDEP-2 cells suggesting that CTCF could play a B-ALL cell line specific role in maintaining MYC expression.


Assuntos
Fator de Ligação a CCCTC/fisiologia , Cromatina/ultraestrutura , Elementos Facilitadores Genéticos/genética , Regulação Leucêmica da Expressão Gênica , Genes myc , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-myc/biossíntese , Fator de Ligação a CCCTC/deficiência , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Cromatina/genética , Regulação para Baixo , Células Precursoras Eritroides/metabolismo , Técnicas de Introdução de Genes , Genes Reporter , Humanos , Conformação de Ácido Nucleico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Transcriptoma
5.
Genome Biol ; 20(1): 50, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30867008

RESUMO

BACKGROUND: Sequencing errors are key confounding factors for detecting low-frequency genetic variants that are important for cancer molecular diagnosis, treatment, and surveillance using deep next-generation sequencing (NGS). However, there is a lack of comprehensive understanding of errors introduced at various steps of a conventional NGS workflow, such as sample handling, library preparation, PCR enrichment, and sequencing. In this study, we use current NGS technology to systematically investigate these questions. RESULTS: By evaluating read-specific error distributions, we discover that the substitution error rate can be computationally suppressed to 10-5 to 10-4, which is 10- to 100-fold lower than generally considered achievable (10-3) in the current literature. We then quantify substitution errors attributable to sample handling, library preparation, enrichment PCR, and sequencing by using multiple deep sequencing datasets. We find that error rates differ by nucleotide substitution types, ranging from 10-5 for A>C/T>G, C>A/G>T, and C>G/G>C changes to 10-4 for A>G/T>C changes. Furthermore, C>T/G>A errors exhibit strong sequence context dependency, sample-specific effects dominate elevated C>A/G>T errors, and target-enrichment PCR led to ~ 6-fold increase of overall error rate. We also find that more than 70% of hotspot variants can be detected at 0.1 ~ 0.01% frequency with the current NGS technology by applying in silico error suppression. CONCLUSIONS: We present the first comprehensive analysis of sequencing error sources in conventional NGS workflows. The error profiles revealed by our study highlight new directions for further improving NGS analysis accuracy both experimentally and computationally, ultimately enhancing the precision of deep sequencing.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/normas , Neoplasias/genética , Reação em Cadeia da Polimerase/normas , Análise de Sequência de DNA/normas , Software , Estudos de Casos e Controles , Humanos , Mutação , Controle de Qualidade
6.
Bioprocess Biosyst Eng ; 42(4): 631-642, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30607611

RESUMO

Deinococcus xibeiensis R13 was isolated from an extreme environment in Xinjiang, China, and can resist gamma-radiation and UV-irradiation. In this study, D. xibeiensis R13 was shown to be capable of efficiently producing carotenoids in culture, and factors influencing its productivity were identified. The maximum carotenoid yield was observed at an initial temperature of 30 °C and pH 7.0 in the presence of fructose, tryptone at a C/N ratio of 1:5, and 10 µM Fe2+. The carotenoid yield under modified culture conditions was 6.64 mg/L after fermentation for 48 h, representing an increase of 84% compared to the original conditions. The biomass reached 7.22 g/L, which was 2.19-fold higher than under non-optimized conditions. The produced carotenoids were extracted from R13 and analyzed by UPLC-MS. This is the first study of carotenoid production by the new strain D. xibeiensis R13, which provides a new source for the microbial fermentation of natural carotenoids, and also provides a good reference for industrial production of other carotenoids and other terpenoid products.


Assuntos
Biomassa , Carotenoides/biossíntese , Deinococcus/crescimento & desenvolvimento , Raios Ultravioleta , Microbiologia Industrial/métodos
7.
Microb Pathog ; 128: 178-183, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30610900

RESUMO

Janthinobacterium sp. B9-8, isolated from low temperature-sewage in Xinjiang, China, is capable of producing violacein, a promising antibiotic. Here we report the genome sequence of B9-8, which consist of 4,726,850 bp with a G + C content of 48.72%. The violacein biosynthesis gene cluster vioABCDE was identified and analyzed based on the genomic data, which revealed relatively low query coverage (3-44%) and identity (66-87%) with existing strains. Janthinobacterium sp. B9-8 grew fast and reached a high cell density and violacein content within 24 h at 25 °C. The availability of this genome sequence will greatly benefit the industrial production of violacein and facilitate supplementary studies on the mechanism for violacein biosynthesis.


Assuntos
Temperatura Baixa , Indóis/metabolismo , Oxalobacteraceae/genética , Oxalobacteraceae/isolamento & purificação , Oxalobacteraceae/metabolismo , Esgotos/microbiologia , Sequenciamento Completo do Genoma , Sequência de Aminoácidos , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Composição de Bases , Sequência de Bases , China , Cromossomos Bacterianos , Genes Bacterianos/genética , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Família Multigênica/genética , Oxalobacteraceae/classificação , RNA Ribossômico 16S/genética , Alinhamento de Sequência
8.
AMB Express ; 8(1): 94, 2018 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-29860613

RESUMO

Deinococcus wulumuqiensis R12 is a red-pigmented extremophilic microorganism with powerful antioxidant properties that was isolated from radiation-contaminated soil in Xinjiang Uyghur Autonomous Region of China. The key carotenoid biosynthesis genes, crtE, crtB and crtI, which are related to the cells' antioxidant defense, were identified in the sequenced genome of R12 and analyzed. In order to improve the carotenoid yield in engineered Escherichia coli, the origin of carotenoid biosynthesis genes was discussed, and a strain containing the R12 carotenoid biosynthesis genes was constructed to produce lycopene, an important intermediate in carotenoid metabolism. The gene order and fermentation conditions, including the culture medium, temperature, and light, were optimized to obtain a genetically engineered strain with a high lycopene production capacity. The highest lycopene content was 688 mg L-1 in strain IEB, which corresponds to a 2.2-fold improvement over the original recombinant strain EBI.

9.
Oncotarget ; 6(19): 17065-80, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-26158411

RESUMO

Esophageal Squamous Cell Carcinoma (ESCC) is among the most common malignant cancers worldwide. In the past, extensive efforts have been made to characterize the involvement of protein-coding genes in ESCC tumorigenesis but few for long noncoding RNAs (lncRNAs). To investigate the transcriptome profile and functional relevance of lncRNAs, we performed an integrative analysis of a customized combined lncRNA-mRNA microarray and RNA-seq data on ESCCs and matched normal tissues. We identified numerous lncRNAs that were differentially expressed between the normal and tumor tissues, termed "ESCC-associated lncRNAs (ESCALs)", of which, the majority displayed restricted expression pattern. Also, a subset of ESCALs appeared to be associated with ESCC patient survival. Gene set enrichment analysis (GSEA) further suggested that over half of the ESCALs were positively-or negatively-associated with metastasis. Among these, we identified a novel nuclear-retained lncRNA, named Epist, which is generally highly expressed in esophagus, and which is down-regulated during ESCC progression. Epist over-expression and knockdown studies further suggest that Epist inhibits the metastasis, acting as a tumor suppressor in ESCC. Collectively, our analysis of the ESCC transcriptome identified the potential tumor suppressing lncRNA Epist, and provided a foundation for future efforts to identify functional lncRNAs for cancerous therapeutic targeting.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , RNA Longo não Codificante/genética , Northern Blotting , Carcinoma de Células Escamosas/mortalidade , Transformação Celular Neoplásica/genética , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Estimativa de Kaplan-Meier , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcriptoma
10.
Cancer Lett ; 350(1-2): 34-42, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24769072

RESUMO

In this study, we analyzed the microRNA (miRNA) expression profile of 119 paired ESCC samples by microarray and identified a four-miRNA signature that predicted patient survival. The signature derived from the training set (n=60) had a good prognostic value in the test set (n=59) and the independent cohort (n=58), indicating the replicability of its prognostic value. Furthermore, the stratified analysis showed that the signature could predict the survival of TNM stage II and stage III patients, indicating that the four-miRNA signature could help to more accurately predict ESCC patient survival.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sobrevida
11.
Gut ; 63(11): 1700-10, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24522499

RESUMO

BACKGROUND: Oesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles. OBJECTIVE: To assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs. METHOD: LncRNA expression profiles were studied by microarray in paired tumour and normal tissues from 119 patients with OSCC and validated by qRT-PCR. The 119 patients were divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random Forest supervised classification algorithm and a nearest shrunken centroid algorithm, then validated in a test group and further, in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis. RESULTS: LncRNAs showed significantly altered expression in OSCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885.1, XLOC_013014 and ENST00000547963.1) which classified the patients into two groups with significantly different overall survival (median survival 19.2 months vs >60 months, p<0.0001). The signature was applied to the test group (median survival 21.5 months vs >60 months, p=0.0030) and independent cohort (median survival 25.8 months vs >48 months, p=0.0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with OSCC. Stratified analysis suggested that the signature was prognostic within clinical stages. CONCLUSIONS: Our results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , RNA Longo não Codificante/metabolismo , Biomarcadores Tumorais/fisiologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Transcriptoma/fisiologia
12.
J Cell Biochem ; 114(9): 2160-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23553990

RESUMO

Copy number variation (CNV) and abnormal expression of microRNAs (miRNAs) always lead to deregulation of genes in cancer, including gastric cancer (GC). However, little is known about how CNVs affect the expression of miRNAs. By integrating CNV and miRNA profiles in the same samples, we identified eight miRNAs (miR-1274a, miR-196b, miR-4298, miR-181c, miR-181d, miR-23a, miR-27a and miR-24-2) that were located in the amplified regions and were upregulated in GC. In particular, amplification of miR-23a-27a-24-2 cluster and miR-181c-181d cluster frequently occurred at 19p13.13 and were confirmed by genomic real-time PCR in another 25 paired GC samples. Moreover, in situ hybridization (ISH) experiments represented that mature miR-23a was increased in GCs (75.5%, 40/53) compared with matched normal tissues (28.6%, 14/49, P = 0.001). Knocking down of miR-23a expression inhibited BGC823 cell growth in vitro and in vivo. In addition, the potential target genes of miR-23a were investigated by integration of mRNA profile and miRNA TargetScan predictions, we found that upregulation of miR-23a and downregulation of metallothionein 2A (MT2A) were detected simultaneously in 70% (7/10) of the miRNA and mRNA profiles. Furthermore, an inverse correlation between miR-23a and MT2A expression was detected in GCs and normal tissues. Through combining luciferase assay, we confirmed that MT2A is a potential target of miR-23a. In conclusion, these results suggest that integration of CNV-miRNA-mRNA profiling is a powerful tool for identifying molecular signatures, and that miR-23a might play a role in regulating MT2A expression in GC.


Assuntos
Metalotioneína/metabolismo , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Biologia Computacional , Humanos , Imuno-Histoquímica , Hibridização In Situ , Metalotioneína/genética , Camundongos , Camundongos Nus , MicroRNAs/genética , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/genética
13.
BMC Mol Biol ; 13: 5, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22333459

RESUMO

BACKGROUND: The human papillomavirus (HPV) E2 protein is a multifunctional DNA-binding protein. The transcriptional activity of HPV E2 is mediated by binding to its specific binding sites in the upstream regulatory region of the HPV genomes. Previously we reported a HPV-2 variant from a verrucae vulgaris patient with huge extensive clustered cutaneous, which have five point mutations in its E2 ORF, L118S, S235P, Y287H, S293R and A338V. Under the control of HPV-2 LCR, co-expression of the mutated HPV E2 induced an increased activity on the viral early promoter. In the present study, a series of mammalian expression plasmids encoding E2 proteins with one to five amino acid (aa) substitutions for these mutations were constructed and transfected into HeLa, C33A and SiHa cells. RESULTS: CAT expression assays indicated that the enhanced promoter activity was due to the co-expressions of the E2 constructs containing A338V mutation within the DNA-binding domain. Western blots analysis demonstrated that the transiently transfected E2 expressing plasmids, regardless of prototype or the A338V mutant, were continuously expressed in the cells. To study the effect of E2 mutations on its DNA-binding activity, a serial of recombinant E2 proteins with various lengths were expressed and purified. Electrophoresis mobility shift assays (EMSA) showed that the binding affinity of E2 protein with A338V mutation to both an artificial probe with two E2 binding sites or HPV-2 and HPV-16 promoter-proximal LCR sequences were significantly stronger than that of the HPV-2 prototype E2. Furthermore, co-expression of the construct containing A338V mutant exhibited increased activities on heterologous HPV-16 early promoter P97 than that of prototype E2. CONCLUSIONS: These results suggest that the mutation from Ala to Val at aa 338 is critical for E2 DNA-binding and its transcriptional regulation.


Assuntos
Alphapapillomavirus/metabolismo , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Mutação Puntual , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Linhagem Celular , DNA/química , Proteínas de Ligação a DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Papillomavirus Humano 16/genética , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Proteínas Oncogênicas Virais/genética , Regiões Promotoras Genéticas , Ligação Proteica , Estrutura Terciária de Proteína , Transcrição Genética
14.
BMC Bioinformatics ; 12: 208, 2011 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-21612673

RESUMO

BACKGROUND: Development of effective scoring functions is a critical component to the success of protein structure modeling. Previously, many efforts have been dedicated to the development of scoring functions. Despite these efforts, development of an effective scoring function that can achieve both good accuracy and fast speed still presents a grand challenge. RESULTS: Based on a coarse-grained representation of a protein structure by using only four main-chain atoms: N, Cα, C and O, we develop a knowledge-based scoring function, called NCACO-score, that integrates different structural information to rapidly model protein structure from sequence. In testing on the Decoys'R'Us sets, we found that NCACO-score can effectively recognize native conformers from their decoys. Furthermore, we demonstrate that NCACO-score can effectively guide fragment assembly for protein structure prediction, which has achieved a good performance in building the structure models for hard targets from CASP8 in terms of both accuracy and speed. CONCLUSIONS: Although NCACO-score is developed based on a coarse-grained model, it is able to discriminate native conformers from decoy conformers with high accuracy. NCACO is a very effective scoring function for structure modeling.


Assuntos
Aminoácidos/química , Modelos Moleculares , Proteínas/química , Bases de Dados de Proteínas , Proteínas/metabolismo
15.
PLoS One ; 6(2): e17215, 2011 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-21365008

RESUMO

Fold recognition, or threading, is a popular protein structure modeling approach that uses known structure templates to build structures for those of unknown. The key to the success of fold recognition methods lies in the proper integration of sequence, physiochemical and structural information. Here we introduce another type of information, local structural preference potentials of 3-residue and 9-residue fragments, for fold recognition. By combining the two local structural preference potentials with the widely used sequence profile, secondary structure information and hydrophobic score, we have developed a new threading method called FR-t5 (fold recognition by use of 5 terms). In benchmark testings, we have found the consideration of local structural preference potentials in FR-t5 not only greatly enhances the alignment accuracy and recognition sensitivity, but also significantly improves the quality of prediction models.


Assuntos
Reconhecimento Automatizado de Padrão/métodos , Conformação Proteica , Engenharia de Proteínas/métodos , Dobramento de Proteína , Sequência de Aminoácidos/fisiologia , Biologia Computacional/métodos , Bases de Dados de Proteínas , Interações Hidrofóbicas e Hidrofílicas , Modelos Biológicos , Modelos Moleculares , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/química , Estrutura Secundária de Proteína , Análise de Sequência de Proteína/métodos
16.
Bioinformatics ; 27(6): 785-90, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21216772

RESUMO

MOTIVATION: Side-chain modeling has seen wide applications in computational structure biology. Most of the popular side-chain modeling programs explore the conformation space using discrete rigid rotamers for speed and efficiency. However, in the tightly packed environments of protein interiors, these methods will inherently lead to atomic clashes and hinder the prediction accuracy. RESULTS: We present a side-chain modeling method (CIS-RR), which couples a novel clash-detection guided iterative search (CIS) algorithm with continuous torsion space optimization of rotamers (RR). Benchmark testing shows that compared with the existing popular side-chain modeling methods, CIS-RR removes atomic clashes much more effectively and achieves comparable or even better prediction accuracy while having comparable computational cost. We believe that CIS-RR could be a useful method for accurate side-chain modeling. AVAILABILITY: CIS-RR is available to non-commercial users at our website: http://jianglab.ibp.ac.cn/lims/cisrr/cisrr.html.


Assuntos
Algoritmos , Biologia Computacional/métodos , Modelos Moleculares , Proteínas/química , Conformação Proteica , Software
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 24(11): 1391-4, 2004 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15762485

RESUMO

Fluorimetric method has been proposed for the speciation of Al in natural waters, based on the different competitive complexation behavior of analytical reagent and natural organic matter to Al. With eriochrome blue black R (EBBR) or morin, the monomeric inorganic Al (Al(i)) was determined, while with 8-hydroxylquinoline, the total monomeric Al (Al(a)) was obtained. The analytical results of Al speciation in natural water are close to those by Driscoll's method. The method is simple and reliable. Fractionation of Al was realized by selecting appropriate reagents under the pH of natural water determined. The merits of this novel strategy are that the disturbance to original equilibrium of Al species is minimized and the results conform to the actual situation of natural waters.


Assuntos
Alumínio/isolamento & purificação , Fluorometria/métodos , Água/química , Fracionamento Químico , Água Doce/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água
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