简介:Thereisalargegapbetweenthenumberofmembraneprotein(MP)sequencesandthatoftheirdecoded3Dstructures,especiallyhigh-resolutionstructures,duetodifficultiesincrystalpreparationofMPs.However,detailedknowledgeofthe3DstructureisrequiredforthefundamentalunderstandingofthefunctionofanMPandtheinteractionsbetweentheproteinanditsinhibitorsoractivators.Inthispaper,somecomputationalapproachesthathavebeenusedtopredictMPstructuresarediscussedandcompared.
简介:TheCoronaviridaefamilyischaracterizedbyanucleocapsidthatiscomposedofthegenomeRNAmoleculeincombinationwiththenucleoprotein(Nprotein)withinavirion.ThemoststrikingphysiochemicalfeatureoftheNproteinofSARS-CoVisthatitisatypicalbasicproteinwithahighpredictedpIandhighhydrophilicity,whichisconsistentwithitsfunctionofbindingtotheribophosphatebackboneoftheRNAmolecule.ThepredictedhighextentofphosphorylationoftheNproteinonmultiplecandidatephosphorylationsitesdemonstratesthatitwouldberelatedtoimportantfunctions,suchasRNA-bindingandlocalizationtothenucleolusofhostcells.SubsequentstudyshowsthatthereisanSR-richregionintheNproteinandthisregionmightbeinvolvedintheprotein-proteininteraction.TheabundantantigenicsitespredictedintheNprotein,aswellasexperimentalevidencewithsynthesizedpolypeptides,indicatethattheNproteinisoneofthemajorantigensoftheSARS-CoV.Comparedwithotherviralstructuralproteins,thelowvariationrateoftheNproteinwithregardstoitssizesuggestsitsimportancetothesurvivalofthevirus.
简介:象从应用Biosys-tems的AB1700站台那样的新奇微数组技术在信号答应重要增加为微弱地表示的抄本的动态范围和更高的敏感。我们把AB1700数据的一个代表性的集合与同样代表性的AffymetrixHG-U133A数据集作比较。AB1700设计扩大信号在由一个数量级的更低的界限的动态察觉范围。这些高敏感的数据的日志正常信号分发侧面需要被二独立分布表示。另外的秒分发盖住将用Affymetrix技术变未被发现的那些抄本。在AB1700数据的信号依赖者变化分发是信号紧张的重要功能,用合成功能可记述。这些高敏感的transcriptome侧面的急速地不同的结构要求改编或甚至标准微数组分析方法的重新开发。基于统计性质,我们为为如此的开发是必要的AB1700数据导出一个信号变化分发模型。有趣地,在AB1700数据观察的双木头正常分发反映抄写开始的二根本上不同的生物学的机制。
简介:Predictingprotein-codinggenesstillremainsasignificantchallenge.Althoughavarietyofcomputationalprogramsthatusecommonlymachinelearningmethodshaveemerged,theaccuracyofpredictionsremainsalowlevelwhenimplementinginlargegenomicsequences.Moreover,computationalgenefindinginnewlyse-quencedgenomesisespeciallyadifficulttaskduetotheabsenceofatrainingsetofabundantvalidatedgenes.Herewepresentanewgene-findingprogram,SCGPred,toimprovetheaccuracyofpredictionbycombiningmultiplesourcesofevidence.SCGPredcanperformbothsupervisedmethodinpreviouslywell-studiedgenomesandunsupervisedoneinnovelgenomes.BytestingwithdatasetscomposedoflargeDNAsequencesfromhumanandanovelgenomeofUstilagomaydi,SCG-Predgainsasignificantimprovementincomparisontothepopularabinitiogenepredictors.WealsodemonstratethatSCGPredcansignificantlyimprovepredic-tioninnovelgenomesbycombiningseveralforeigngenefinderswithsimilarityalignments,whichissuperiortootherunsupervisedmethods.Therefore,SCG-Predcanserveasanalternativegene-findingtoolfornewlysequencedeukaryoticgenomes.Theprogramisfreelyavailableathttp://bio.scu.edu.cn/SCGPred/.
简介:Inourpreviousstudies,DAZAP2geneexpressionwasdown-regulatedinuntreatedpatientsofmultiplemyeloma(MM).ForbetterstudyingthestructureandfunctionofDAZAP2,afull-lengthCdnawasisolatedfrommononuclearcellsofanormalhumanbonemarrow,sequencedanddepositedtoGenbank(AY430097).ThissequencehasanidenticalORF(openreadingframe)astheNM_014764fromhumantestisandtheD31767fromhumancelllineKG-1.PhylogeneticanalysisandstructurepredictionrevealthatDAZAP2homologuesarehighlyconservedthroughoutevolutionandshareapolyprolineregionandseveralpotentialSH2/SH3bindingsites.DAZAP2occursasasingle-copygenewithafour-exonorganization.WefurthernoticedthatthefunctionalDAZAP2geneislocatedonChromosome12anditspseudogenegeneisonChromosome2withelectroniclocationofhumanchromosomeinGenbank,thoughnogeneticabnormalitiesofMMhavebeenreportedonChromosome12.TheORFofhumanDAZAP2encodesa17-kDaprotein,whichishighlysimilartomousePrtb.TheDAZAP2proteinismainlylocalizedincytoplasmwithadiscretepatternofpunctuateddistribution.DAZAP2mayassociatewithcarcinogenesisofMMandparticipateinyet-to-beidentifiedsignalingpathwaystoregulateproliferationanddifferentiationofplasmacells.
简介:陷阱,SLD5的heterotetramer,PSF1,PSF2,和PSF3蛋白质,一个新兴的染色质因素被认出涉及开始和DNA复制的延伸步。尽管酵母和Xenopus陷阱基因很好被记录,他们在更高的优核质的orthologous基因充分没被描绘。在这研究,我们报导genomic结构和哺乳动物的陷阱基因的transcriptional规定。浆液刺激在人的房间增加了GINSmRNA层次。用通常认为的陷阱倡导者序列的记者基因试金表明哺乳动物的陷阱的表示被17beta-Estradiol-stimulated雌激素受体高山调整哈,并且人的PSF3充当对抄写因素E2F1应答的基因。这研究的目标是介绍当前的数据以便在哺乳动物的房间在陷阱基因规定和函数的领域里鼓励进一步的工作。
简介:Inthepost-genomicera,variouscomputationalmethodsthatpredictprotein-proteininteractionsatthegenomelevelareavailable;however,eachmethodhasitsownadvantagesanddisadvantages,resultinginfalsepredictions.Herewedevel-opedauniqueintegratedapproachtoidentifyinteractingpartner(s)ofSemaphorin5A(SEMA5A),beginningwithsevenproteinssharingsimilarligandinteractingresiduesasputativebindingpartners.ThemethodsincludeDwyerandRoot-Bernstein/Dillontheoriesofproteinevolution,hydropathiccomplementarityofproteinstructure,patternofproteinfunctionsamongmolecules,informationondomain-domaininteractions,co-expressionofgenesandproteinevolution.AmongthesetofsevenproteinsselectedasputativeSEMA5Ainteractingpartners,wefoundthefunctionsofPlexinB3andNeuropilin-2tobeassociatedwithSEMA5A.WemodeledthesemaphorindomainstructureofPlexinB3andfoundthatitsharessimilaritywithSEMA5A.Moreover,avirtualexpressiondatabasesearchandRT-PCRanalysisshowedco-expressionofSEMA5AandPlexinB3andtheseproteinswerefoundtohaveco-evolved.Inaddition,weconfirmedtheinterac-tionofSEMA5AwithPlexinB3inco-immunoprecipitationstudies.Overall,thesestudiesdemonstratethatanintegratedmethodofpredictioncanbeusedatthegenomelevelfordiscoveringmanyunknownproteinbindingpartnerswithknownligandbindingdomains.
简介:TheR(replicase)proteinistheuniquelydefinednon-structuralprotein(NSP)responsibleforRNAreplication,mutationrateorfidelity,regulationoftranscrip-tionincoronavirusesandmanyotherssRNAviruses.Basedonourcompletegenomesequencesoffourisolates(BJ01-BJ04)ofSARS-CoVfromBeijing,China,weanalyzedthestructureandpredictedfunctionsoftheRproteinincomparisonwith13otherisolatesofSARS-CoVand6othercoronaviruses.TheentireORF(open-readingframe)encodesfortwomajorenzymeactivities,RNA-dependentRNApolymerase(RdRp)andproteinaseactivities.TheRpolyproteinunder-goesacomplexproteolyticprocesstoproduce15function-relatedpeptides.Ahydrophobicdomain(HOD)andahydrophilicdomain(HID)arenewlyidentifiedwithinNSP1.ThesubstitutionrateoftheRproteinisclosetotheaverageoftheSARS-CoVgenome.ThefunctionaldomainsinallNSPsoftheRproteingivedifferentphylogeneticresultsthatsuggesttheirdifferentmutationrateunderselectivepressure.ElevenhighlyconservedregionsinRdRpandtwelvecleavagesitesby3CLP(chymotrypsin-likeprotein)havebeenidentifiedaspotentialdrugtargets.Findingssuggestthatitispossibletoobtaininformationaboutthephy-logenyofSARS-CoV,aswellaspotentialtoolsfordrugdesign,genotypinganddiagnosticsofSARS.