QRB Discovery最新文献_第8页

Homologous basic helix-loop-helix transcription factors induce distinct deformations of torsionally-stressed DNA: a potential transcription regulation mechanism. 同源的基本螺旋-环-螺旋转录因子诱导扭转应力DNA的明显变形:一种潜在的转录调节机制。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.5

Johanna Hörberg, Kevin Moreau, Anna Reymer

{"title":"Homologous basic helix-loop-helix transcription factors induce distinct deformations of torsionally-stressed DNA: a potential transcription regulation mechanism.","authors":"Johanna Hörberg, Kevin Moreau, Anna Reymer","doi":"10.1017/qrd.2022.5","DOIUrl":"https://doi.org/10.1017/qrd.2022.5","url":null,"abstract":"Changing torsional restraints on DNA is essential for the regulation of transcription. Torsional stress, introduced by RNA polymerase, can propagate along chromatin facilitating topological transitions and modulating the specific binding of transcription factors (TFs) to DNA. Despite the importance, the mechanistic details on how torsional stress impacts the TFs-DNA complexation remain scarce. Herein, we address the impact of torsional stress on DNA complexation with homologous human basic helix-loop-helix (BHLH) hetero- and homodimers: MycMax, MadMax and MaxMax. The three TF dimers exhibit specificity towards the same DNA consensus sequence, the E-box response element, while regulating different transcriptional pathways. Using microseconds-long atomistic molecular dynamics simulations together with the torsional restraint that controls DNA total helical twist, we gradually over- and underwind naked and complexed DNA to a maximum of ± 5°/bp step. We observe that the binding of the BHLH dimers results in a similar increase in DNA torsional rigidity. However, under torsional stress the BHLH dimers induce distinct DNA deformations, characterised by changes in DNA grooves geometry and a significant asymmetric DNA bending. Supported by bioinformatics analyses, our data suggest that torsional stress may contribute to the execution of differential transcriptional programs of the homologous TFs by modulating their collaborative interactions.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":"e4"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modelling peptide-protein complexes: docking, simulations and machine learning. 建模肽-蛋白复合物:对接，模拟和机器学习。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.14

Arup Mondal, Liwei Chang, Alberto Perez

引用次数: 5

Graph deep learning locates magnesium ions in RNA. 图深度学习在RNA中定位镁离子。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.17

Yuanzhe Zhou, Shi-Jie Chen

{"title":"Graph deep learning locates magnesium ions in RNA.","authors":"Yuanzhe Zhou, Shi-Jie Chen","doi":"10.1017/qrd.2022.17","DOIUrl":"https://doi.org/10.1017/qrd.2022.17","url":null,"abstract":"Magnesium ions (Mg2+) are vital for RNA structure and cellular functions. Present efforts in RNA structure determination and understanding of RNA functions are hampered by the inability to accurately locate Mg2+ ions in an RNA. Here we present a machine-learning method, originally developed for computer visual recognition, to predict Mg2+ binding sites in RNA molecules. By incorporating geometrical and electrostatic features of RNA, we capture the key ingredients of Mg2+-RNA interactions, and from deep learning, predict the Mg2+ density distribution. Five-fold cross-validation on a dataset of 177 selected Mg2+-containing structures and comparisons with different methods validate the approach. This new approach predicts Mg2+ binding sites with notably higher accuracy and efficiency. More importantly, saliency analysis for eight different Mg2+ binding motifs indicates that the model can reveal critical coordinating atoms for Mg2+ ions and ion-RNA inner/outer-sphere coordination. Furthermore, implementation of the model uncovers new Mg2+ binding motifs. This new approach may be combined with X-ray crystallography structure determination to pinpoint the metal ion binding sites.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9622248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Amyloid-like Hfq interaction with single-stranded DNA: involvement in recombination and replication in Escherichia coli. 淀粉样蛋白Hfq与单链DNA的相互作用:参与大肠杆菌的重组和复制。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.15

Krzysztof Kubiak, Frank Wien, Indresh Yadav, Nykola C Jones, Søren Vrønning Hoffmann, Eric Le Cam, Antoine Cossa, Frederic Geinguenaud, Johan R C van der Maarel, Grzegorz Węgrzyn, Véronique Arluison

{"title":"Amyloid-like Hfq interaction with single-stranded DNA: involvement in recombination and replication in Escherichia coli.","authors":"Krzysztof Kubiak, Frank Wien, Indresh Yadav, Nykola C Jones, Søren Vrønning Hoffmann, Eric Le Cam, Antoine Cossa, Frederic Geinguenaud, Johan R C van der Maarel, Grzegorz Węgrzyn, Véronique Arluison","doi":"10.1017/qrd.2022.15","DOIUrl":"https://doi.org/10.1017/qrd.2022.15","url":null,"abstract":"Interactions between proteins and single-stranded DNA (ssDNA) are crucial for many fundamental biological processes, including DNA replication and genetic recombination. Thus, understanding detailed mechanisms of these interactions is necessary to uncover regulatory rules occurring in all living cells. The RNA-binding Hfq is a pleiotropic bacterial regulator that mediates many aspects of nucleic acid metabolism. The protein notably mediates mRNA stability and translation efficiency by using stress-related small regulatory RNA as cofactors. In addition, Hfq helps to compact double-stranded DNA. In this paper, we focused on the action of Hfq on ssDNA. A combination of experimental methodologies, including spectroscopy and molecular imaging, has been used to probe the interactions of Hfq and its amyloid C-terminal region with ssDNA. Our analysis revealed that Hfq binds to ssDNA. Moreover, we demonstrate for the first time that Hfq drastically changes the structure and helical parameters of ssDNA, mainly due to its C-terminal amyloid-like domain. The formation of the nucleoprotein complexes between Hfq and ssDNA unveils important implications for DNA replication and recombination.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":"e15"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10283214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

A novel statistical method predicts mutability of the genomic segments of the SARS-CoV-2 virus. 一种新的统计方法预测了SARS-CoV-2病毒基因组片段的易变性。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2021.13

Amir Hossein Darooneh, Michelle Przedborski, Mohammad Kohandel

{"title":"A novel statistical method predicts mutability of the genomic segments of the SARS-CoV-2 virus.","authors":"Amir Hossein Darooneh, Michelle Przedborski, Mohammad Kohandel","doi":"10.1017/qrd.2021.13","DOIUrl":"https://doi.org/10.1017/qrd.2021.13","url":null,"abstract":"The SARS-CoV-2 virus has made the largest pandemic of the 21st century, with hundreds of millions of cases and tens of millions of fatalities. Scientists all around the world are racing to develop vaccines and new pharmaceuticals to overcome the pandemic and offer effective treatments for COVID-19 disease. Consequently, there is an essential need to better understand how the pathogenesis of SARS-CoV-2 is affected by viral mutations and to determine the conserved segments in the viral genome that can serve as stable targets for novel therapeutics. Here, we introduce a text-mining method to estimate the mutability of genomic segments directly from a reference (ancestral) whole genome sequence. The method relies on calculating the importance of genomic segments based on their spatial distribution and frequency over the whole genome. To validate our approach, we perform a large-scale analysis of the viral mutations in nearly 80,000 publicly available SARS-CoV-2 predecessor whole genome sequences and show that these results are highly correlated with the segments predicted by the statistical method used for keyword detection. Importantly, these correlations are found to hold at the codon and gene levels, as well as for gene coding regions. Using the text-mining method, we further identify codon sequences that are potential candidates for siRNA-based antiviral drugs. Significantly, one of the candidates identified in this work corresponds to the first seven codons of an epitope of the spike glycoprotein, which is the only SARS-CoV-2 immunogenic peptide without a match to a human protein.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":"e1"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8795775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9912917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Computational drug discovery under RNA times. RNA时代的计算药物发现。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.20

Mattia Bernetti, Riccardo Aguti, Stefano Bosio, Maurizio Recanatini, Matteo Masetti, Andrea Cavalli

引用次数: 2

Resolving the fine structure in the energy landscapes of repeat proteins. 解析重复蛋白能量格局中的精细结构。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.4

Murilo N Sanches, R Gonzalo Parra, Rafael G Viegas, Antonio B Oliveira, Peter G Wolynes, Diego U Ferreiro, Vitor B P Leite

{"title":"Resolving the fine structure in the energy landscapes of repeat proteins.","authors":"Murilo N Sanches, R Gonzalo Parra, Rafael G Viegas, Antonio B Oliveira, Peter G Wolynes, Diego U Ferreiro, Vitor B P Leite","doi":"10.1017/qrd.2022.4","DOIUrl":"https://doi.org/10.1017/qrd.2022.4","url":null,"abstract":"Ankyrin (ANK) repeat proteins are coded by tandem occurrences of patterns with around 33 amino acids. They often mediate protein-protein interactions in a diversity of biological systems. These proteins have an elongated non-globular shape and often display complex folding mechanisms. This work investigates the energy landscape of representative proteins of this class made up of 3, 4 and 6 ANK repeats using the energy-landscape visualisation method (ELViM). By combining biased and unbiased coarse-grained molecular dynamics AWSEM simulations that sample conformations along the folding trajectories with the ELViM structure-based phase space, one finds a three-dimensional representation of the globally funnelled energy surface. In this representation, it is possible to delineate distinct folding pathways. We show that ELViMs can project, in a natural way, the intricacies of the highly dimensional energy landscapes encoded by the highly symmetric ankyrin repeat proteins into useful low-dimensional representations. These projections can discriminate between multiplicities of specific parallel folding mechanisms that otherwise can be hidden in oversimplified depictions.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":"e7"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Abnormal methylation in the NDUFA13 gene promoter of breast cancer cells breaks the cooperative DNA recognition by transcription factors. 乳腺癌细胞NDUFA13基因启动子甲基化异常破坏了转录因子对DNA的协同识别。

QRB Discovery Pub Date : 2022-01-01 DOI: 10.1017/qrd.2022.21

Johanna Hörberg, Björn Hallbäck, Kevin Moreau, Anna Reymer

{"title":"Abnormal methylation in the NDUFA13 gene promoter of breast cancer cells breaks the cooperative DNA recognition by transcription factors.","authors":"Johanna Hörberg, Björn Hallbäck, Kevin Moreau, Anna Reymer","doi":"10.1017/qrd.2022.21","DOIUrl":"https://doi.org/10.1017/qrd.2022.21","url":null,"abstract":"Selective DNA binding by transcription factors (TFs) is crucial for the correct regulation of DNA transcription. In healthy cells, promoters of active genes are hypomethylated. A single CpG methylation within a TF response element (RE) may change the binding preferences of the protein, thus causing the dysregulation of transcription programs. Here, we investigate a molecular mechanism driving the downregulation of the NDUFA13 gene, due to hypermethylation, which is associated with multiple cancers. Using bioinformatic analyses of breast cancer cell line MCF7, we identify a hypermethylated region containing the binding sites of two TFs dimers, CEBPB and E2F1-DP1, located 130 b.p. from the gene transcription start site. All-atom extended MD simulations of wild type and methylated DNA alone and in complex with either one or both TFs dimers provide mechanistic insights into the cooperative asymmetric binding order of the two dimers; the CEBPB binding should occur first to facilitate the E2F1-DP1-DNA association. The CpG methylation within the E2F1-DP1 RE and the linker decrease the cooperativity effects and renders the E2F1-DP1 binding site less recognizable by the TF dimer. Taken together, the identified CpG methylation site may contribute to the downregulation of the NDUFA13 gene.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"3 ","pages":"e23"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Erratum: Effect of Relative Humidity on Hydrogen Peroxide Production in Water Droplets - CORRIGENDUM. 更正：相对湿度对水滴中过氧化氢生成的影响 - 更正。

QRB Discovery Pub Date : 2021-11-04 eCollection Date: 2021-01-01 DOI: 10.1017/qrd.2021.11

Maria T Dulay, Carlos Alberto Huerta-Aguilar, Christian F Chamberlayne, Richard N Zare, Adriaan Davidse, Sinisa Vukovic

引用次数: 0

Effect of relative humidity on hydrogen peroxide production in water droplets. 相对湿度对水滴中过氧化氢生成的影响。

QRB Discovery Pub Date : 2021-07-27 eCollection Date: 2021-01-01 DOI: 10.1017/qrd.2021.6

Maria T Dulay, Carlos Alberto Huerta-Aguilar, Christian F Chamberlayne, Richard N Zare, Adriaan Davidse, Sinisa Vukovic

{"title":"Effect of relative humidity on hydrogen peroxide production in water droplets.","authors":"Maria T Dulay, Carlos Alberto Huerta-Aguilar, Christian F Chamberlayne, Richard N Zare, Adriaan Davidse, Sinisa Vukovic","doi":"10.1017/qrd.2021.6","DOIUrl":"10.1017/qrd.2021.6","url":null,"abstract":"Mist is generated by ultrasonic cavitation of water (Fisher Biograde, pH 5.5-6.5) at room temperature (20-25 °C) in open air with nearly constant temperature (22-25 °C) but varying relative humidity (RH; 24-52%) over the course of many months. Water droplets in the mist are initially about 7 μm in diameter at about 50% RH. They are collected, and the concentration of hydrogen peroxide (H2O2) is measured using commercial peroxide test strips and by bromothymol blue oxidation. The quantification method is based on the Fenton chemistry of dye degradation to determine the oxidation capacity of water samples that have been treated by ultrasonication. It is found that the hydrogen peroxide concentration varies nearly linearly with RH over the range studied, reaching a low of 2 parts per million (ppm) at 24% RH and a high of 6 ppm at 52% RH. Some possible public health implications concerning the transmission of respiratory viral infections are suggested for this threefold change in H2O2 concentration with RH.","PeriodicalId":34636,"journal":{"name":"QRB Discovery","volume":"2 ","pages":"e8"},"PeriodicalIF":0.0,"publicationDate":"2021-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/ae/S2633289221000065a.PMC10392617.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0