Detecting distant homology with meta-BASIC

Detecting distant homology with meta-BASIC
Detecting distant homology with meta-BASIC

Detecting distant homology with Meta-BASIC

Krzysztof Ginalski 1,3,*,Marcin von Grotthuss 4,Nick V.Grishin 1,2and Leszek Rychlewski 3

1

Department of Biochemistry and 2Howard Hughes Medical Institute,University of Texas,Southwestern Medical Center,5323Harry Hines Boulevard,Dallas,Texas 75390-9038,USA,3BioInfoBank Institute,ul.Limanowskiego 24A,

60-744Poznan

′,Poland and 4Faculty of Physics,Adam Mickiewicz University,ul.Umultowska 85,61-614Poznan

′,Poland Received January 31,2004;Revised and Accepted March 9,2004

ABSTRACT

Meta-BASIC (http://basic.bioinfo.pl)is a novel sensit-ive approach for recognition of distant similarity

between proteins based on consensus alignments of meta profiles.Specifically,Meta-BASIC compares sequence profiles combined with predicted second-ary structure by utilizing several scoring systems and alignment algorithms.In our benchmarking tests,Meta-BASIC outperforms many individual servers,including fold recognition servers,and it can compete with meta predictors that base their strength on the structural comparison of models.In addition,Meta-BASIC,which enables detection of very distant relationships even if the tertiary structure for the reference protein is not known,has a high-throughput capability.This new method is applied to 860PfamA protein families with unknown function (DUF)and provides many novel structure–functional assign-ments available on-line at http://basic.bioinfo.pl/duf.pl.Detailed discussion is provided for two of the most interesting assignments.DUF271and DUF431are predicted to be a nucleotide-diphospho-sugar transferase and an a /b -knot SAM-dependent RNA methyltransferase,respectively.

INTRODUCTION

The fastest approach to annotating a novel protein is to infer its function from an experimentally studied homologue.How-ever,simple and reliable sequence similarity search tools such as Fasta (1)or Blast (2)are frequently not powerful enough to detect homology unambiguously.In the 1990s threading methods (3–6)emerged,which were able to go further in predicting similarities between proteins,but only when one of the proteins to be aligned had a known

three-dimensional (3D)structure.Threading methods were developed with the hope of detecting analogues,i.e.structu-rally similar proteins with no evolutionary relationship.How-ever,for most predictions found by threading,homology (evolutionary relationship)was later supported by new and advanced sequence comparison methods,such as PSI-Blast (7).The competition and partnership between sequence-based and structure-based prediction strategies has led to con-siderable improvements and changes in recent years.The fold recognition ?eld is now dominated by the meta predictors [3D-Jury (8),Pcons (9),Shotgun (10),Libullela (11)]exploiting many different prediction methods of both types to generate consensus models.The usage of pro?les is now generalized to the alignment of two sequence pro?les (12–18)or two meta pro?les [ORFeus (19)].Here we present a method,Meta-BASIC (Bilaterally Ampli?ed Sequence Information Compar-ison),that combines the achievements in sequence pro?le-based strategies with secondary structure predictions to gen-erate fast and reliable predictions using meta pro?le alignment algorithms.We apply Meta-BASIC to obtain large-scale structure–functional predictions for catalogued protein families of unknown function in the Pfam database (20)and ?nd many surprising functional connections.This shows the general applicability of the method,which,similar to structural geno-mic initiatives,is aimed at extracting functional information from poorly studied protein sequences.METHODS

Overview

Our method,Meta-BASIC,derives its strength from four sources.First,it is a novel sequence pro?le-based method.Pro?le methods,including PSI-Blast,set the standard in the ?eld as accurate predictors of remote links between proteins.High-scoring PSI-Blast hits are essentially correct and biolo-gically meaningful.In addition,a skilful PSI-Blast user is able to pick a few non-trivial homologues by careful analysis of hits in the twilight zone.However,many interesting but very

*To whom correspondence should be addressed at BioInfoBank Institute,ul.Limanowskiego 24A,60-744Poznan

′,Poland.Tel:+48618653520;Fax:+48618643350;Email:kginal@bioinfo.pl

Correspondence may also be addressed to Leszek Rychlewski.Email:leszek@bioinfo.pl

The online version of this article has been published under an open access https://www.360docs.net/doc/c115838538.html,ers are entitled to use,reproduce,disseminate,or display the open access version of this article provided that:the original authorship is properly and fully attributed;the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given;if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated.a2004,the authors

Nucleic Acids Research,Vol.32,Web Server issue aOxford University Press 2004;all rights reserved

W576–W581Nucleic Acids Research,2004,Vol.32,Web Server issue DOI:10.1093/nar/gkh370

remote homologues still remain undetected at the sequence level.Second,Meta-BASIC uses predicted local structure (secondary structure)information.Adding structural informa-tion to a sequence pro?le often helps to?nd homologues that diverge beyond recognition sequence-wise but remain structu-rally similar.In contrast to Meta-BASIC,many conventional threading algorithms utilize experimental global3D structure to score similarity.Therefore,as a pre-requisite for correct predic-tion,a protein of interest must have the structure of its homo-logue https://www.360docs.net/doc/c115838538.html,ing predicted secondary structure,we are free from that requirement and can?nd links between proteins of unknownstructure.Inaddition,partingwiththeglobalthreading allowsforafasteralgorithmandhigherthroughput.Third,Meta-BASIC not only combines sequence pro?le with secondary structure pro?le to form what we call meta pro?le,but also utilizes several scoring systems and alignment algorithms. Averaging between the results obtained by slightly different approaches helps to boost the accuracy.Fourth,Meta-BASIC has a high-throughput capability since it is a stand-alone pro-gram in contrast to most meta servers,which collect predictions from several remotely located prediction services. Algorithm

In brief,the current version of Meta-BASIC(BasD)uses two versions of highly sensitive similarity detection algorithms. Both algorithms are based on dynamic programming and gapped alignment of meta pro?les.Speci?cally,meta pro?les combine the conventional positional variability of amino acids (sequence pro?les)with secondary structure predictions.Our recent studies demonstrated that alignment of meta pro?les as implemented in ORFeus is more sensitive than the alignment of pure sequence pro?les(19).As a further improvement of this approach,Meta-BASIC uses the combination of two main com-ponents that differ in the way the score for aligning two posi-tions of meta pro?les is calculated.The?rst method(zdotc) computes a dot product of sequence variability vectors for the two positions,while the second method(zmatc)multiplies one vector by the BLOSUM62matrix and the result by the other vector.The predicted preferences for the three secondary struc-ture states(a-helix,b-strand and loop)are compared using the city block metric(the sum of the absolute differences of pro-pensities).Alignment scores obtained with both versions are normalized to enable direct comparison.To ensure standardi-zation,each pro?le is aligned to a set of300unrelated pro?les and the collected scores are used to estimate the parameters of the distribution of random scores.Each alignment score is then converted to a Z-score by subtracting the mean of the distribu-tion and dividing the result by the standard deviation.The?nal score reported by Meta-BASIC is equal to the average of the two Z-scores obtained with both methods,and the alignment is selected from the version which reported higher Z-score.A more detailed description of Meta-BASIC is available on-line at http://basic.bioinfo.pl/about.pl.

RESULTS AND DISCUSSION

Comparison with other methods

Meta-BASIChasbeenextensivelyevaluatedandcomparedwith other protein structure prediction methods in the framework of the LiveBench program(http://bioinfo.pl/LiveBench/)(21). Methods that are being continuously evaluated by LiveBench cover pure sequence algorithms,threading approaches,and various meta predictors that combine sequence-based and structure-based methods.Several meta servers obtain many models generated for the target protein from diverse predic-tion servers that may be located in several countries around the world.These meta servers compare the models with each other to?nd a consensus.All benchmarks,including the recent CASP5experiment(22),con?rm that consensus-based methods that use many prediction servers are more powerful than individual servers and thus represent the best of what researchers can explore today.However, these meta servers are slow since they need to collect models from many sources.

The main asset of Meta-BASIC is the high speci?city of the reported con?dence score,which means that very few high-scoring hits represent incorrect predictions.Importantly, 12different components and3different versions of Meta-BASIC were tested in the LiveBench-8experiment to?nally select BasD as having the highest speci?city(Table1).Our benchmarking of Meta-BASIC reveals that it outperforms many individual servers,including fold recognition servers, and it can compete with meta predictors basing their strength on the structural comparison of models.Speci?cally, Meta-BASIC(BasD)has achieved rank2in the speci?city assessment in LiveBench-8.Only one version of Shotgun meta predictor,Shotgun-on-3(3DS3),has obtained a higher speci?city.While competitive in accuracy with other meta predictors,Meta-BASIC has clear advantages.It is local, relatively fast and can be used for high-throughput annotation of genomes(1000predictions per day are feasible on the current server at http://basic.bioinfo.pl),while the meta pre-dictors coupled to the Meta Server(23)can handle only about50predictions per day.Another crucial advantage is that Meta-BASIC does not require the structure of the tem-plate to be known.This makes it possible to compare the target protein not only with proteins of known structure,such as those extracted from the PDB(24),but also with protein families of unknown structure,such as those from Pfam database,various genomic resources or any other sequence databases.

Structure–functional annotation for uncharacterized protein families

Exploiting this positive aspect of the new method,we searched for putative homologues for860PfamA protein families without functional annotation(DUF,catalogued by Pfam developers)to generate hypotheses about the functions of these proteins.Each target family was compared with all 6249PfamA families and with7225proteins(representatives at90%of sequence identity)extracted from PDB.For each PDB entry and PfamA/DUF family(represented as consensus sequence),sequence alignments utilized in the pro?le building were created with PSI-Blast,while secondary structure pre-dictions were obtained using the PSIPRED program(25).The same comparison was also conducted using RPS-Blast and PSI-Blast(combined with Meta-Blast).Meta-BASIC was able to?nd signi?cant hits to PfamA for208families and signi?cant hits to PDB for155families,when the conservative

Nucleic Acids Research,2004,Vol.32,Web Server issue W577

Z-score of12was used as a threshold.Predictions with Z-score above12have<5%probability of being incorrect(using rigorous structural criteria).Of those hits,70%can be con-?rmed with signi?cant Meta-Blast E-value of<0.005,and85% achieved E-value of<10(Figure1).As a necessary disclaimer, these statistics may change,since all DUF families are recal-culated periodically to keep the database of assignments up to date with regard to the currently available sequential and structural information.When the Meta-BASIC threshold is relaxed to lower values,many more potential links can be found,but in such cases additional evidence is necessary to con?rm the validity of the predictions.All predictions are available on-line at http://basic.bioinfo.pl/duf.pl and in our opinion represent a goldmine for undiscovered homologies. Detection of unexpected but relatively reliable relationships enables researchers to assign function,and frequently also a structure,to a few completely uncharacterized families of hypothetical proteins.Table2shows selected examples of such unexpected assignments obtained(in October2003)with Meta-BASIC score above12that could not be con?rmed by PSI-Blast or RPS-Blast in our setting.Table2includes also the highest scoring Meta-BASIC matches to proteins of known structure.All of the?ve hits have con?dent fold assignments

as con?rmed by detailed manual analysis and all?ve provide unexpected functional predictions to the best of our knowledge not reported before.Two of the?ve predictions are discussed below.It should also be stressed that in several cases where no reliable structural assignments were obtained,Meta-BASIC (but not Meta-Blast)con?dently mapped analysed DUF families to other PfamA families of unknown structure.For instance,DUF820was linked by Meta-BASIC with Z-score of 21.74to the Competence protein CoiA-like family(PF06054). This further emphasizes the applicability of the new method to detecting distant relationship between proteins even if the tertiary structure for the reference protein is not known.Prediction highlights

DUF271belongs to the superfamily of nucleotide-diphospho-sugar transferases.PfamA family DUF271encompasses several hypothetical proteins from Caernorhabditis elegans. While Meta-Blast was unable to?nd any reliable matches to other PfamA families or to proteins of known structure,Meta-BASIC predicted the nucleotide-diphospho-sugar transferases fold for this family.Meta-BASIC assigned reliable scores to Glycosyl transferase family8(GT8)(PF01501)and,in parti-cular,to the structures of galactosyl transferase LgtC(26)and Glycogenin-1(27).Apart from LgtC and Glycogenin,

PF01501 Figure1.Statistics of putative annotations obtained with Meta-BASIC for860 PfamA families of unknown function.The figure shows the number of similarities found with Meta-BASIC between the target families with unknown function(DUF)and other PfamA families or PDB proteins with a conservative Meta-BASIC score cut-off of12(BASIC).The bars labelled ‘Blast’indicate the number of similarities found with Meta-BASIC and supported by Meta-Blast with an E-value below10or0.005,respectively. The Meta-Blast E-values correspond to the lowest E-values reported by PSI-Blast or RPS-Blast.

https://www.360docs.net/doc/c115838538.html,parison of3Meta-BASIC versions and12components in LiveBench-8

EASY Score Hits HARD Score Hits ROC Score rdotb600267mBAS230634BasD92.0 zdotb597168BasD226133rorfc92.0 mBAS596468rorfc223332zmatc90.9 BasP595867zdotb222532mBAS90.1 BasD595168zdotc221332zorfc89.4 rdotc593268BasP215731zdotc88.7 zmatb590968zorfc215031zdotb87.9 zdotc590868rorfb214431zmatb87.9 zmatc588668rdotb214330rorfb87.7 rorfc588068rdotc212531BasP87.6 rorfb587566zmatc206330rdotc85.6 zorfb586966zorfb203029zorfb83.5 zorfc586168zmatb199630rmatc81.8 rmatb584367rmatb197328rdotb79.5 rmatc582268rmatc190227rmatb76.7 The targets are divided into EASY and HARD.The‘Score’columns for both categories show the total score obtained with the3D-eval evaluation method.The‘Hits’columns indicate the number of correct hits produced by the methods.The specificity of the methods is evaluated in the ROC column.A higher ROC score indicates a higher reliability of the confidence score generated by each method.The details of the evaluation procedure are described on the LiveBench pages(http://bioinfo.pl/ LiveBench/)and in related publications.Three tested Meta-BASIC versions are shown in boldface.There are three basic component methods dot,orf and mat.orf and dot use dot product calculation when comparing two vectors of the aligned profiles.mat uses vector times matrix times vector multiplication to compare the two vectors.Methods with names starting with the letter r return the raw score of the alignment while methods starting with the letter z return the Z-score transformation of the raw score.Methods with names ending with letter b use three PSI-Blast iterations to calculate the profile for each family while methods with names ending with the letter c use six PSI-Blast iterations.mBAS calculates the score by averaging the results obtained with all six methods which return Z-scores(zorfb,zorfc,zdotb,zdotc, zmatb,zmatc).The underlying raw scores cannot be easily compared with each other.BasP uses only zdotb and zmatb(three PSI-Blast iterations).BasD uses zdotc and zmatc(six PSI-Blast iterations)and it was selected as the current version of Meta-BASIC.

W578Nucleic Acids Research,2004,Vol.32,Web Server issue

contains about 200different proteins involved in the biosyn-thesis of disaccharides,oligosaccharides and polysaccharides.The GT8enzymes belong to the EC 2.4.1group that catalyse the transfer of sugar moieties from activated donor molecules (UDP-sugar)to speci?c acceptor molecules,forming glyco-sidic bonds (28,29).The consensus sequence of DUF271con-tains four known motifs that are necessary for UDP-sugar binding (Figure 2).The ?rst conserved motif (33YDSSN 37)is responsible for the interaction between the enzyme and the nucleotide.Conserved Asp34forms a hydrogen bond with the nitrogen of the uracil base (27).The DUF271also contains the DXD-like motif (129QQD 131)that is conserved in most prokaryotic and eukaryotic glycosyltransferases.This motif appears to function primarily in the coordination of the divalent cation,most commonly Mn 2+,essential for the binding of the nucleotide sugar-donor substrate (26).Asp202,is the next key residue that is highly conserved among all DUF271sequences.The 40and 60sugar oxygens make hydro-gen bonds to the side-chain carboxylate of Asp202,indicat-ing that this residue has an important role in binding and most

likely in catalysis as well.The fourth sequence motif (243QLDGEKK 249)forms hydrogen bonds with Mn 2+and both phosphates.Gln243possibly coordinates the cation while the backbone nitrogen of conserved Gly246and the side-chain of conserved Lys249directly interact with the phosphates.Therefore,based on the conservation of residues characteristic for the uridine 50-diphosphate-sugar (UDP-sugar)binding site,the glycosyltransferase function can be con?dently inferred for DUF271.

DUF431belongs to the superfamily of a /b -knot SAM-dependent RNA methyltransferases.DUF431,encompassing several hypothetical proteins from Saccharomyces cerevisiae ,Plasmodium falciparum ,Plasmodium yoelii ,Neurospora crassa and a few archeal organisms,is another PfamA family for which no reliable structure–functional assignment can be obtained with PSI-Blast or RPS-Blast.Meta-BASIC assigned an above-threshold score to the tRNA m(1)G methyltrans-ferase family (PF04243),which includes biochemically char-acterized S.cerevisiae protein Trm10p responsible for the methylation of G residues to m(1)G in tRNA Gly at position 9(30).In addition,Meta-BASIC mapped the consensus sequence of DUF431to the structures of the cofactor-binding domain of RrmH (31),RlmB (32),YibK (33),YggJ (34)and YbeA,which are members of the SPOUT (35)superfamily of known or predicted S-adenosylmethionine(SAM)-dependent tRNA and rRNA methyltransferases.This domain adopts an a /b -knot fold with topology differing from that of the classical methyltransferases.Importantly,unique pseudoknot structure provides the binding site for SAM,which interacts mainly with the main chain amide and carbonyl groups as well as with the surrounding side-chains of hydrophobic residues that are also conserved in the DUF431family.DUF431and SPOUT methyltransferases share the conserved Gly90in the SAM-binding loop (35),Ala72at the position occupied by tiny side-chains,important for the pseudoknot formation,as well as several conservatively replaced residues at the dimer interface.Despite very weak sequence similarity,conservation of these unique features as well as reasonable mapping of predicted and observed secondary structure elements are additional indic-ators of the correct structure–functional assignment (Figure 3).All these ?ndings demonstrate that DUF431is yet another family of a /b -knot SAM-dependent RNA methyltransferases.In addition,we propose that the last 60residues not mapped on the cofactor-binding domain may form a substrate-binding domain.Its C-terminal localization indicates that DUF431proteins possibly use tRNA as substrates

(33).

Figure 2.DUF271belongs to the superfamily of nucleotide-diphospho-sugar transferases.The 3D model of the DUF271consensus sequence was based on the structure of the galactosyl transferase LgtC (26)(PDB code:1ga8)from Neisseria meningitides .The Mn 2+cation (orange),UDP-sugar (gray)and the side-chains (white)of the key residues (Asp34,Ser36,Gln129,Asp131,Asp202,Gln243,Lys249)essential for UDP-sugar binding are shown.

Table 2.Selected examples of unexpected but reliable Meta-BASIC predictions DUF PfamA Name

Score PDB Name

Score DUF271PF01501Glycosyl transferase family 823.551ll0A Glycogenin-1

23.70DUF431PF04243tRNA m(1)G methyltransferase 17.061ipaA RNA 20-O-Ribose Methyltransferase 10.81DUF393PF00462Glutaredoxin

13.291fovA Glutaredoxin 3

14.16DUF920PF00797N-acetyltransferase 13.021e2tA N-Hydroxyarylamine O-Acetyltransferase 15.57DUF833

PF03577

Peptidase family U34

12.73

3pvaA

Penicillin V Acylase

9.24

Five out of twenty-six significant similarities between PfamA families with unknown function (DUF)and other PfamA families detected by Meta-BASIC but not with Meta-Blast E -value below 10are displayed in left part of the table.The structural assignment for the five families based on detected similarities to proteins of known structure is reported in the right part.In all cases the name of the related family or protein and the Meta-BASIC score is shown.Only first,strongest PfamA and PDB hits are listed.Our literature search indicated that these similarities for the selected DUF families have not been reported before.

Nucleic Acids Research,2004,Vol.32,Web Server issue W579

CONCLUSIONS

The database of potential structure–functional annotations generated by Meta-BASIC for PfamA families of unknown function contains many more examples of non-trivial and potentially useful assignments that can be studied and veri?ed by researchers.Methods such as Meta-BASIC that push homology inference further and allow for large-scale annota-tions may represent a cheaper alternative to,and clearly complement,many experimental efforts in the diverse ?eld of genomics-oriented research.The growing amounts of data obtained in large-scale sequencing projects,structural genomics efforts,DNA-chip experiments,two-hybrid interac-tion mapping and many others provide the foundation for,and a strong boost to,the systematic approach to investigating cells and organisms [systems biology (36)].To fully understand the large networks of interactions,it is crucial to know as much as possible about every individual member of the system.Yet,functional annotation of proteins with standard methods leaves a prohibitively large gap of more than 30%of the proteome.The goal of Meta-BASIC is to reduce this gap and we hope that scientists annotating genomes will take advantage of the recent progress in the ?eld of protein structure–functional prediction.ACKNOWLEDGEMENTS

This work was supported by 5th Framework Project Grants and KBN grants ELM (QLRI-CT2000-00127E-617/SPB/5.PR UE/DZ 438/2003-2004)and MiFriend (QLR3-CT2000-00170E-617/SPB/5.PR UE/DZ 439/2003),and an NIH grant GM67165to N.V.G.REFERENCES

1.Pearson,W.R.and Lipman,D.J.(1988)Improved tools for biological sequence comparison.Proc.Natl Acad.Sci.,USA ,85,2444–2448.

2.Altschul,S.F.,Gish,W.,Miller,W.,Myers,E.W.and Lipman,D.J.(1990)Basic local alignment search tool.J.Mol.Biol.,215,403–410.

3.Narayana,S.V.and Argos,P.(1984)Residue contacts in protein structures and implications for protein folding.Int.J.Pept.Protein Res.,24,25–39.

4.Bowie,J.U.,Luthy,R.and Eisenberg,D.(1991)A method to identify protein sequences that fold into a known three-dimensional structure.Science ,253,164–170.

5.Blundell,T.L.(1991)Comparative analysis of protein three-dimensional structures and an approach to the inverse folding problem.Ciba Found.Symp.,161,28–36;discussion 37–51.

6.Godzik,A.,Kolinski,A.and Skolnick,J.(1992)Topology fingerprint approach to the inverse protein folding problem.J.Mol.Biol.,227,227–238.

7.Altschul,S.F.,Madden,T.L.,Schaffer,A.A.,Zhang,J.,Zhang,Z.,

Miller,W.and Lipman,D.J.(1997)Gapped BLAST and PSI-BLAST:a new generation of protein database search programs.Nucleic Acids Res.,25,3389–3402.

8.Ginalski,K.,Elofsson,A.,Fischer,D.and Rychlewski,L.(2003)3D-Jury:a simple approach to improve protein structure predictions.Bioinformatics ,19,1015–1018.

9.Lundstrom,J.,Rychlewski,L.,Bujnicki,J.and Elofsson,A.(2001)Pcons:a neural-network-based consensus predictor that improves fold recognition.Protein Sci.,10,2354–2362.

10.Fischer,D.(2003)3D-SHOTGUN:a novel,cooperative,fold-recognition

meta-predictor.Proteins ,51,434–441.

11.Juan,D.,Grana,O.,Pazos,F.,Fariselli,P.,Casadio,R.and Valencia,A.

(2003)A neural network approach to evaluate fold recognition results.Proteins ,50,600–608.

12.von Ohsen,N.,Sommer,I.and Zimmer,R.(2003)Profile-profile

alignment:a powerful tool for protein structure prediction.Pac.Symp.Biocomput.,252–263.

13.Sadreyev,R.and Grishin,N.(2003)COMPASS:a tool for comparison of

multiple protein alignments with assessment of statistical significance.J.Mol.Biol.,326,317–336.

14.Panchenko,A.R.(2003)Finding weak similarities between proteins by

sequence profile comparison.Nucleic Acids Res.,31,683–689.15.Yona,G.and Levitt,M.(2002)Within the twilight zone:a sensitive

profile-profile comparison tool based on information theory.J.Mol.Biol.,315,1257–1275.

16.Heger,A.and Holm,L.(2001)Picasso:generating a covering set of

protein family profiles.Bioinformatics ,17,272–279.

17.Rychlewski,L.,Jaroszewski,L.,Li,W.and Godzik,A.(2000)Comparison

of sequence profiles.Strategies for structural predictions using sequence information.Protein Sci.,9,232–241.

18.Rychlewski,L.,Zhang,B.and Godzik,A.(1998)Fold and function

predictions for Mycoplasma genitalium proteins.Fold Des.,3,229–238.19.Ginalski,K.,Pas,J.,Wyrwicz,L.S.,von Grotthuss,M.,Bujnicki,J.M.and

Rychlewski,L.(2003)ORFeus:Detection of distant homology using sequence profiles and predicted secondary structure.Nucleic Acids Res.,31,3804–3807.

20.Bateman,A.,Birney,E.,Cerruti,L.,Durbin,R.,Etwiller,L.,Eddy,S.R.,

Griffiths-Jones,S.,Howe,K.L.,Marshall,M.and Sonnhammer,E.L.(2002)The Pfam protein families database.Nucleic Acids Res.,30,276–280.

21.Rychlewski,L.,Fischer,D.and Elofsson,A.(2003)LiveBench-6:large-scale automated evaluation of protein structure prediction servers.Proteins ,53(Suppl.6),542–547.

22.Kinch,L.N.,Wrabl,J.O.,Krishna,S.S.,Majumdar,I.,Sadreyev,R.I.,

Qi,Y.,Pei,J.,Cheng,H.and Grishin,N.V.(2003)CASP5assessment of fold recognition target predictions.Proteins ,53(Suppl.6),395–409.23.Bujnicki,J.M.,Elofsson,A.,Fischer,D.and Rychlewski,L.(2001)

Structure prediction meta server.Bioinformatics ,17,750–751.24.Berman,H.M.,Westbrook,J.,Feng,Z.,Gilliland,G.,Bhat,T.N.,

Weissig,H.,Shindyalov,I.N.and Bourne,P.E.(2000)The Protein Data Bank.Nucleic Acids Res.,28,235–242.

25.Jones,D.T.(1999)Protein secondary structure prediction based on

position-specific scoring matrices.J.Mol.Biol.,292,195–202.

26.Persson,K.,Ly,H.D.,Dieckelmann,M.,Wakarchuk,W.W.,Withers,S.G.

and Strynadka,N.C.(2001)Crystal structure of the retaining

galactosyltransferase LgtC from Neisseria meningitidis in complex with donor and acceptor sugar analogs.Nat.Struct.Biol.,8,166–175.27.Gibbons,B.J.,Roach,P.J.and Hurley,T.D.(2002)Crystal structure

of the autocatalytic initiator of glycogen biosynthesis,glycogenin.J.Mol.Biol.,319,

463–477.

Figure 3.DUF431belongs to the superfamily of a /b -knot SAM-dependent RNA methyltransfeases.The 3D model of the cofactor-binding domain of the DUF431consensus sequence was based on the structure of the YibK,hypothetical tRNA/rRNA methyltransferase HI0766(33)(PDB code:1mxi)from Haemophilus influenzae .The pseudoknot is coloured in violet.The S-adenosylhomocysteine (SAH)(grey)and positions of highly conserved residues (red dots)essential for the pseudoknot formation (Ala72)and SAH binding (Gly90)are shown.

W580Nucleic Acids Research,2004,Vol.32,Web Server issue

28.Campbell,J.A.,Davies,G.J.,Bulone,V.and Henrissat,B.(1997)A

classification of nucleotide-diphospho-sugar glycosyltransferases

based on amino acid sequence similarities.Biochem.J.,326,

929–939.

29.Campbell,J.A.,Davies,G.J.,Bulone,V.V.and Henrissat,B.

(1998)A classification of nucleotide-diphospho-sugar

glycosyltransferases based on amino acid sequence similarities.

Biochem.J.,329,719.

30.Jackman,J.E.,Montange,R.K.,Malik,H.S.and Phizicky,E.M.(2003)

Identification of the yeast gene encoding the tRNA m1G

methyltransferase responsible for modification at position9.RNA,

9,574–585.

31.Nureki,O.,Shirouzu,M.,Hashimoto,K.,Ishitani,R.,Terada,T.,

Tamakoshi,M.,Oshima,T.,Chijimatsu,M.,Takio,K.,Vassylyev,D.G.

et al.(2002)An enzyme with a deep trefoil knot for the active-site

architecture.Acta Crystallogr.D Biol.Crystallogr.,58,1129–1137. 32.Michel,G.,Sauve,V.,Larocque,R.,Li,Y.,Matte,A.and Cygler,M.(2002)

The structure of the RlmB23S rRNA methyltransferase reveals a

new methyltransferase fold with a unique knot.Structure(Camb),

10,1303–1315.

33.Lim,K.,Zhang,H.,Tempczyk,A.,Krajewski,W.,Bonander,N.,Toedt,J.,

Howard,A.,Eisenstein,E.and Herzberg,O.(2003)Structure of the YibK

methyltransferase from Haemophilus influenzae(HI0766):a cofactor

bound at a site formed by a knot.Proteins,51,56–67.

34.Forouhar,F.,Shen,J.,Xiao,R.,Acton,T.B.,Montelione,G.T.and Tong,L.

(2003)Functional assignment based on structural analysis:Crystal

structure of the yggJ protein(HI0303)of Haemophilus influenzae reveals

an RNA methyltransferase with a deep trefoil knot.Proteins,

53,329–332.

35.Anantharaman,V.,Koonin,E.V.and Aravind,L.(2002)SPOUT:

a class of methyltransferases that includes spoU and trmD RNA

methylase superfamilies,and novel superfamilies of predicted

prokaryotic RNA methylases.J.Mol.Microbiol.Biotechnol.,

4,71–75.

36.Hood,L.and Galas,D.(2003)The digital code of DNA.Nature,

421,444–448.

Nucleic Acids Research,2004,Vol.32,Web Server issue W581

With的用法全解

With的用法全解 with结构是许多英语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。本文就此的构成、特点及用法等作一较全面阐述,以帮助同学们掌握这一重要的语法知识。 一、 with结构的构成 它是由介词with或without+复合结构构成,复合结构作介词with或without的复合宾语,复合宾语中第一部分宾语由名词或代词充当,第二部分补足语由形容词、副词、介词短语、动词不定式或分词充当,分词可以是现在分词,也可以是过去分词。With结构构成方式如下: 1. with或without-名词/代词+形容词; 2. with或without-名词/代词+副词; 3. with或without-名词/代词+介词短语; 4. with或without-名词/代词 +动词不定式; 5. with或without-名词/代词 +分词。 下面分别举例: 1、 She came into the room,with her nose red because of cold.(with+名词+形容词,作伴随状语)

2、 With the meal over , we all went home.(with+名词+副词,作时间状语) 3、The master was walking up and down with the ruler under his arm。(with+名词+介词短语,作伴随状语。) The teacher entered the classroom with a book in his hand. 4、He lay in the dark empty house,with not a man ,woman or child to say he was kind to me.(with+名词+不定式,作伴随状语)He could not finish it without me to help him.(without+代词 +不定式,作条件状语) 5、She fell asleep with the light burning.(with+名词+现在分词,作伴随状语) Without anything left in the with结构是许多英 语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。本文就此的构成、特点及用法等作一较全面阐述,以帮助同学们掌握这一重要的语法知识。 二、with结构的用法 with是介词,其意义颇多,一时难掌握。为帮助大家理清头绪,以教材中的句子为例,进行分类,并配以简单的解释。在句子中with结构多数充当状语,表示行为方式,伴随情况、时间、原因或条件(详见上述例句)。 1.带着,牵着…… (表动作特征)。如: Run with the kite like this.

with用法归纳

with用法归纳 (1)“用……”表示使用工具,手段等。例如: ①We can walk with our legs and feet. 我们用腿脚行走。 ②He writes with a pencil. 他用铅笔写。 (2)“和……在一起”,表示伴随。例如: ①Can you go to a movie with me? 你能和我一起去看电影'>电影吗? ②He often goes to the library with Jenny. 他常和詹妮一起去图书馆。 (3)“与……”。例如: I’d like to have a talk with you. 我很想和你说句话。 (4)“关于,对于”,表示一种关系或适应范围。例如: What’s wrong with your watch? 你的手表怎么了? (5)“带有,具有”。例如: ①He’s a tall kid with short hair. 他是个长着一头短发的高个子小孩。 ②They have no money with them. 他们没带钱。 (6)“在……方面”。例如: Kate helps me with my English. 凯特帮我学英语。 (7)“随着,与……同时”。例如: With these words, he left the room. 说完这些话,他离开了房间。 [解题过程] with结构也称为with复合结构。是由with+复合宾语组成。常在句中做状语,表示谓语动作发生的伴随情况、时间、原因、方式等。其构成有下列几种情形: 1.with+名词(或代词)+现在分词 此时,现在分词和前面的名词或代词是逻辑上的主谓关系。 例如:1)With prices going up so fast, we can't afford luxuries. 由于物价上涨很快,我们买不起高档商品。(原因状语) 2)With the crowds cheering, they drove to the palace. 在人群的欢呼声中,他们驱车来到皇宫。(伴随情况) 2.with+名词(或代词)+过去分词 此时,过去分词和前面的名词或代词是逻辑上的动宾关系。

独立主格with用法小全

独立主格篇 独立主格,首先它是一个“格”,而不是一个“句子”。在英语中任何一个句子都要有主谓结构,而在这个结构中,没有真正的主语和谓语动词,但又在逻辑上构成主谓或主表关系。独立主格结构主要用于描绘性文字中,其作用相当于一个状语从句,常用来表示时间、原因、条件、行为方式或伴随情况等。除名词/代词+名词、形容词、副词、非谓语动词及介词短语外,另有with或without短语可做独立主格,其中with可省略而without不可以。*注:独立主格结构一般放在句首,表示原因时还可放在句末;表伴随状况或补充说明时,相当于一个并列句,通常放于句末。 一、独立主格结构: 1. 名词/代词+形容词 He sat in the front row, his mouth half open. Close to the bank I saw deep pools, the water blue like the sky. 靠近岸时,我看见几汪深池塘,池水碧似蓝天。 2. 名词/代词+现在分词 Winter coming, it gets colder and colder. The rain having stopped, he went out for a walk.

The question having been settled, we wound up the meeting. 也可以The question settled, we wound up the meeting. 但含义稍有差异。前者强调了动作的先后。 We redoubled our efforts, each man working like two. 我们加倍努力,一个人干两个人的活。 3. 名词/代词+过去分词 The job finished, we went home. More time given, we should have done the job much better. *当表人体部位的词做逻辑主语时,不及物动词用现在分词,及物动词用过去分词。 He lay there, his teeth set, his hands clenched, his eyes looking straight up. 他躺在那儿,牙关紧闭,双拳紧握,两眼直视上方。 4. 名词/代词+不定式 We shall assemble at ten forty-five, the procession to start moving at precisely eleven. We divided the work, he to clean the windows and I to sweep the floor.

with用法小结

with用法小结 一、with表拥有某物 Mary married a man with a lot of money . 马莉嫁给了一个有着很多钱的男人。 I often dream of a big house with a nice garden . 我经常梦想有一个带花园的大房子。 The old man lived with a little dog on the lonely island . 这个老人和一条小狗住在荒岛上。 二、with表用某种工具或手段 I cut the apple with a sharp knife . 我用一把锋利的刀削平果。 Tom drew the picture with a pencil . 汤母用铅笔画画。 三、with表人与人之间的协同关系 make friends with sb talk with sb quarrel with sb struggle with sb fight with sb play with sb work with sb cooperate with sb I have been friends with Tom for ten years since we worked with each other, and I have never quarreled with him . 自从我们一起工作以来,我和汤姆已经是十年的朋友了,我们从没有吵过架。 四、with 表原因或理由 John was in bed with high fever . 约翰因发烧卧床。 He jumped up with joy . 他因高兴跳起来。 Father is often excited with wine . 父亲常因白酒变的兴奋。 五、with 表“带来”,或“带有,具有”,在…身上,在…身边之意

with的用法

with[wIT] prep.1.与…(在)一起,带着:Come with me. 跟我一起来吧。/ I went on holiday with my friend. 我跟我朋友一起去度假。/ Do you want to walk home with me? 你愿意和我一道走回家吗 2.(表带有或拥有)有…的,持有,随身带着:I have no money with me. 我没有带钱。/ He is a man with a hot temper. 他是一个脾气暴躁的人。/ We bought a house with a garden. 我们买了一座带花园的房子。/ China is a very large country with a long history. 中国是一个具有历史悠久的大国。3.(表方式、手段或工具)以,用:He caught the ball with his left hand. 他用左手接球。/ She wrote the letter with a pencil. 她用铅笔写那封信。4.(表材料或内容)以,用:Fill the glass with wine. 把杯子装满酒。/ The road is paved with stones. 这条路用石头铺砌。5.(表状态)在…的情况下,…地:He can read French with ease. 他能轻易地读法文。/ I finished my homework though with difficulty. 虽然有困难,我还是做完了功课。6.(表让步)尽管,虽然:With all his money, he is unhappy. 尽管他有钱,他并不快乐。/ With all his efforts, he lost the match. 虽然尽了全力,他还是输了那场比赛。7.(表条件)若是,如果:With your permission, I’ll go. 如蒙你同意我就去。8.(表原因或理由)因为,由于:He is tired with work. 他工作做累了。/ At the news we all jumped with joy. 听到这消息我们都高兴得跳了起来。9.(表时间)当…的时候,在…之后:With that remark, he left. 他说了那话就离开了。/ With daylight I hurried there to see what had happened. 天一亮我就去那儿看发生了什么事。10. (表同时或随同)与…一起,随着:The girl seemed to be growing prettier with each day. 那女孩好像长得一天比一天漂亮。11.(表伴随或附带情况)同时:I slept with the window open. 我开着窗户睡觉。/ Don’t speak with your mouth full. 不要满嘴巴食物说话。12.赞成,同意:I am with you there. 在那点上我同你意见一致。13.由…照看,交…管理,把…放在某处:I left a message for you with your secretary. 我给你留了个信儿交给你的秘书了。/ The keys are with reception. 钥匙放在接待处。14 (表连同或包含)连用,包含:The meal with wine came to £8 each. 那顿饭连酒每人8英镑。/ With preparation and marking a teacher works 12 hours a day. 一位老师连备课带批改作业每天工作12小时。15. (表对象或关系)对,关于,就…而言,对…来说:He is pleased with his new house. 他对他的新房子很满意。/ The teacher was very angry with him. 老师对他很生气。/ It’s the same with us students. 我们学生也是这样。16.(表对立或敌对)跟,以…为对手:The dog was fighting with the cat. 狗在同猫打架。/ He’s always arguing with his brother. 他老是跟他弟弟争论。17.(在祈使句中与副词连用):Away with him! 带他走!/ Off with your clothes! 脱掉衣服!/ Down with your money! 交出钱来! 【用法】1.表示方式、手段或工具等时(=以,用),注意不要受汉语意思的影响而用错搭配,如“用英语”习惯上用in English,而不是with English。2.与某些抽象名词连用时,其作用相当于一个副词:with care=carefully 认真地/ with kindness=kindly 亲切地/ with joy=joyfully 高兴地/ with anger=angrily 生气地/ with sorrow=sorrowfully 悲伤地/ with ease=easily 容易地/ with delight=delightedly 高兴地/ with great fluency =very fluently 很流利地3.表示条件时,根据情况可与虚拟语气连用:With more money I would be able to buy it. 要是钱多一点,我就买得起了。/ With better equipment, we could have finished the job even sooner. 要是设备好些,我们完成这项工作还要快些。4.比较with 和as:两者均可表示“随着”,但前者是介词,后者是连词:He will improve as he grows older. 随着年龄的增长,他会进步的。/ People’s ideas change with the change of the times. 时代变了,人们的观念也会变化。5.介词with和to 均可表示“对”,但各自的搭配不同,注意不要受汉语意思的影响而用错,如在kind, polite, rude, good, married等形容词后通常不接介词with而接to。6.复合结构“with+宾语+宾语补足语”是一个很有用的结构,它在句中主要用作状语,表示伴随、原因、时间、条件、方式等;其中的宾语补足语可以是名词、形容词、副词、现在分词、过去分词、不定式、介词短语等:I went out with the windows open. 我外出时没有关窗户。/ He stood before his teacher with his head down. 他低着头站在老师面前。/ He was lying on the bed with all his clothes on. 他和衣躺在床上。/ He died with his daughter yet a schoolgirl. 他去世时,女儿还是个小学生。/ The old man sat there with a basket beside her. 老人坐在那儿,身边放着一个篮子。/ He fell asleep with the lamp burning. 他没熄灯就睡着了。/ He sat there with his eyes closed. 他闭目坐在那儿。/ I can’t go out with all these clothes to wash. 要洗这些衣服,我无法出去了。这类结构也常用于名词后作定语:The boy with nothing on is her son. 没穿衣服的这个男孩子是她儿子。 (摘自《英语常用词多用途词典》金盾出版社) - 1 -

(完整版)with的复合结构用法及练习

with复合结构 一. with复合结构的常见形式 1.“with+名词/代词+介词短语”。 The man was walking on the street, with a book under his arm. 那人在街上走着,腋下夹着一本书。 2. “with+名词/代词+形容词”。 With the weather so close and stuffy, ten to one it’ll rain presently. 天气这么闷热,十之八九要下雨。 3. “with+名词/代词+副词”。 The square looks more beautiful than even with all the light on. 所有的灯亮起来,广场看起来更美。 4. “with+名词/代词+名词”。 He left home, with his wife a hopeless soul. 他走了,妻子十分伤心。 5. “with+名词/代词+done”。此结构过去分词和宾语是被动关系,表示动作已经完成。 With this problem solved, neomycin 1 is now in regular production. 随着这个问题的解决,新霉素一号现在已经正式产生。 6. “with+名词/代词+-ing分词”。此结构强调名词是-ing分词的动作的发出者或某动作、状态正在进行。 He felt more uneasy with the whole class staring at him. 全班同学看着他,他感到更不自然了。 7. “with+宾语+to do”。此结构中,不定式和宾语是被动关系,表示尚未发生的动作。 So in the afternoon, with nothing to do, I went on a round of the bookshops. 由于下午无事可做,我就去书店转了转。 二. with复合结构的句法功能 1. with 复合结构,在句中表状态或说明背景情况,常做伴随、方式、原因、条件等状语。With machinery to do all the work, they will soon have got in the crops. 由于所有的工作都是由机器进行,他们将很快收完庄稼。(原因状语) The boy always sleeps with his head on the arm. 这个孩子总是头枕着胳膊睡觉。(伴随状语)The soldier had him stand with his back to his father. 士兵要他背对着他父亲站着。(方式状语)With spring coming on, trees turn green. 春天到了,树变绿了。(时间状语) 2. with 复合结构可以作定语 Anyone with its eyes in his head can see it’s exactly like a rope. 任何一个头上长着眼睛的人都能看出它完全像一条绳子。 【高考链接】 1. ___two exams to worry about, I have to work really hard this weekend.(04北京) A. With B. Besides C. As for D. Because of 【解析】A。“with+宾语+不定式”作状语,表示原因。 2. It was a pity that the great writer died, ______his works unfinished. (04福建) A. for B. with C. from D.of 【解析】B。“with+宾语+过去分词”在句中作状语,表示状态。 3._____production up by 60%, the company has had another excellent year. (NMET) A. As B.For C. With D.Through 【解析】C。“with+宾语+副词”在句中作状语,表示程度。

with用法

with结构是许多英语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。本文就此的构成、特点及用法等作一较全面阐述,以帮助同学们掌握这一重要的语法知识。 一、with结构的构成 它是由介词with或without+复合结构构成,复合结构作介词with或without的复合宾语,复合宾语中第一部分宾语由名词或代词充当,第二部分补足语由形容词、副词、介词短语、动词不定式或分词充当,分词可以是现在分词,也可以是过去分词。With结构构成方式如下: 1. with或without-名词/代词+形容词; 2. with或without-名词/代词+副词; 3. with或without-名词/代词+介词短语; 4. with或without-名词/代词+动词不定式; 5. with或without-名词/代词+分词。 下面分别举例: 1、She came into the room,with her nose red because of cold.(with+名词+形容词,作伴随状语) 2、With the meal over ,we all went home.(with+名词+副词,作时间状语) 3、The master was walking up and down with the ruler under his arm。(with+名词+介词短语,作伴随状语。)The teacher entered the classroom with a book in his hand. 4、He lay in the dark empty house,with not a man ,woman or child to say he was kind to me.(with+名词+不定式,作伴随状语)He could not finish it without me to help him.(without+代词+不定式,作条件状语) 5、She fell asleep with the light burning.(with+名词+现在分词,作伴随状语) 6、Without anything left in the cupboard,she went out to get something to eat.(without+代词+过去分词,作为原因状语) 二、with结构的用法 在句子中with结构多数充当状语,表示行为方式,伴随情况、时间、原因或条件(详见上述例句)。

【初中英语】with的用法

【With的基本用法与独立主格】 with结构是许多英语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。 一、with结构的构成 它是由介词with或without+复合结构构成,复合结构作介词with或without的复合宾语,复合宾语中第一部分宾语由名词或代词充当,第二部分补足语由形容词、副词、介词短语、动词不定式或分词充当,分词可以是现在分词,也可以是过去分词。With结构构成方式如下: 1. with或without-名词/代词+形容词; 2. with或without-名词/代词+副词; 3. with或without-名词/代词+介词短语; 4. with或without-名词/代词+动词不定式; 5. with或without-名词/代词+分词。 下面分别举例: 1、She came into the room,with her nose red because of cold.(with+名词+形容词,作伴随状语) 2、With the meal over, we all went home.(with+名词+副词,作时间状语) 3、The master was walking up and down with the ruler under his arm。(with+名词+介词短语,作伴随状语。) 4、He could not finish it without me to help him.(without+代词+不定式,作条件状语) 5、She fell asleep with the light on.(with+名词+现在分词,作伴随状语) 二、with结构的用法 with是介词,其意义颇多,一时难掌握。为帮助大家理清头绪,以教材中的句子为例,进行分类,并配以简单的解释。在句子中with结构多数充当状语,表示行为方式,伴随情况、时间、原因或条件(详见上述例句)。 1. 带着,牵着……(表动作特征)。如: Run with the kite like this. 2. 附加、附带着……(表事物特征)。如: A glass of apple juice, two glasses of coke, two hamburgers with potato chips, rice and fish. 3. 和……(某人)一起。 a. 跟某人一起(居住、吃、喝、玩、交谈……) 。如: Now I am in China with my parents. Sometimes we go out to eat with our friends. He / She's talking with a friend. b. 跟go, come 连用,有"加入"到某方的意思。如: Do you want to come with me? 4. 和play一起构成短语动词play with 意为"玩耍……,玩弄……" 如: Two boys are playing with their yo-yos. 5. 与help 一起构成help...with...句式,意为"帮助(某人) 做(某事)"。如: On Monday and Wednesday, he helps his friends with their English. 6. 表示面部神情,有“含着……,带着……”如: "I'm late for school," said Sun Y ang, with tears in his eyes. 7. 表示"用……" 如:

介词with的用法

介词with的用法 1.表示人与人的协同关系,意为“一起”“和” go with 与..一起去 play with 与...一起玩 live with 与...一起住/生活 work with 与...一起工作 make friends with 与....交朋友 talk with sb = talk to sb fight with 与...打架/战斗 cooperate with 与...一起合作 2.表示“带有”“拥有” tea with honey 加蜂蜜的茶 a man with a lot of money 一个有很多钱的人 a house with a big garden 一个带有大花园的房子 a chair with three legs 一张三条腿的椅子 a girl with golden hair 金发的女孩 3.表示“用”某种工具或手段 write with a pencil 用铅笔写字 cut the apple with a knife 用刀切苹果 4.表示“在...身边”“在...身上” I don’t have any money with me. 我身上没带钱。 Take an umbrella with you in case it rains 带把伞以防下雨。 5.表示“在...之下” With the help of sb = with one’s help 在某人的帮助下 6.表示“随着” with the development of ... 随着...的发展 float with the wind 随风飘动

7.常见带有with的动词短语 agree with sb/sth 同意某人或某事deal with sth = do with sth 处理某事 help sb with sth 在...上帮助某人 fall in love with sb/sth 爱上某人/某物 get on with sb 与某人相处 get on well with sb 与某人相处得好 have nothing to do with sb 与某人无关compare A with B 将A和B作比较communicate with sb 与某人交流 argue with sb = quarrel with sb 与某人吵架Have fun with sth 玩的开心 Get away with sth 做坏事不受惩罚 Chat with sb 跟某人闲谈 Charge sb with sth 指控某人。。。 Put up with sth 忍受 8.常见带with的形容词固定搭配 be satisfied with 对...满意 be content with sth 对...满足 be angry with sb 生某人的气 be strict with sb 对某人严格 be patient with sb 对某人有耐心 be popular with sb 受某人欢迎 be filled with sth 装满... 充满..... = be full of sth What’s wrong/the matter with sb/sth be familiar with sb/sth 熟悉某人或某物 be connected with sb/sth 与....有关 Be decorated with 被。。。装饰 Be impressed with/by

with用法归纳

with用法归纳 (1)“用……”表示使用工具,手段等。例如: ①We canwalkwith ourlegsandfeet. 我们用腿脚行走。 ②Hewrites withapencil。她用铅笔写。 (2)“与……在一起”,表示伴随。例如: ①Can you gotoamovie with me?您能与我一起去瞧电影’>电影不? ②He often goes to thelibrarywithJenny、她常与詹妮一起去图书馆。 (3)“与……"。例如: I'd like to have a talk with you、我很想与您说句话、 (4)“关于,对于”,表示一种关系或适应范围。例如: What’s wrong with yourwatch?您得手表怎么了? (5)“带有,具有"。例如: ①He's a tallkid withshort hair. 她就是个长着一头短发得高个子小孩。 ②Theyhaveno money with them、她们没带钱。 (6)“在……方面”。例如: Kate helpsme with myEnglish. 凯特帮我学英语。 (7)“随着,与……同时”、例如: With thesewords, he lefttheroom、说完这些话,她离开了房间。[解题过程] with结构也称为with复合结构。就是由with+复合宾语组成。常在句中做状语,表示谓语动作发生得伴随情况、时间、原因、方式等。其构成有下列几种情形: 1。with+名词(或代词)+现在分词 此时,现在分词与前面得名词或代词就是逻辑上得主谓关系。 例如:1)Withprices going up so fast, we can’t afford luxuries、由于物价上涨很快,我们买不起高档商品。(原因状语) 2)Withthe crowds cheering, they drove to thepalace。 在人群得欢呼声中,她们驱车来到皇宫、(伴随情况) 2、with+名词(或代词)+过去分词

with结构及用法

with 结构 一:with结构的形式 它是由介词with或without+复合结构构成,复合结构作介词with或without的复合宾语,复合宾语中第一部分宾语由名词或代词充当,第二部分补足语由形容词、副词、介词短语、动词不定式或分词充当,分词可以是现在分词,也可以是过去分词。With结构构成方式如下: 1. with或without 名词/代词 例句:Yesterday I saw Mary with a gun. 2. with或without 名词/代词+ 形容词 例句:He is used to sleeping with the windows open. 3. with或without 名词/代词+ 副词 例句:She left the room with all the lights on. 4. with或without 名词/代词+ 介词短语 例句:He walked into the dark street with a stick in his hand. 5. with或without 名词/代词+ 动词不定式 例句:With so much work to do, I have no time for a holiday. 6. with或without 名词/代词+ Ving 例句:We found the house easily with the little boy leading the way.(现在分词表示主动动作,即分词所表示的动作是由with后的宾语发出来的) 7. with或without 名词/代词+ Ved With all the things bought, she went home happily.(过去分词表示被动,with后面的宾语与过去分词之间是被动关系) 8. with或without 名词/代词+ 补语 例句:Possibly this person died without anyone knowing where the coins were hidden. He wondered if he could slide out of the lecture hall without anyone noticing (him). 9. with或without 名词/代词+ 动词不定式和+ Ving/Ved的区别 加不定式是指将要进行的动作,加分词是指主动或被动动作. 10. with+名词/代词+名词 例句:He died with his daughter a schoolgirl. 他在他女儿是个小学生的时候死了 二:with复合结构的句法功能 1. with 复合结构,在句中表状态或说明背景情况该结构常做伴随、方式、原因、条件等状语。 例句:With machinery to do all the work, they will soon have got in the crops. 由于所有的工作都是由机器进行,他们将很快收完庄稼。(原因状语) The boy always sleeps with his head on the arm. 这个孩子总是头枕着胳膊睡觉。(伴随状语) The soldier had him stand with his back to his father. 士兵要他背对着他父亲站着。(方式状语)With spring coming on, trees turn green. 春天到了,树变绿了。(时间状语) 2. with复合结构可以作定语 Anyone with its eyes in his head can see it’s exactly like a rope. 任何一个头上长着眼睛的人都能看出它完全像一条绳子。

with的用法大全

with的用法大全 with结构是许多英语复合结构中最常用的一种。学好它对学好复合宾语结构、不定式复合结构、动名词复合结构和独立主格结构均能起很重要的作用。本文就此的构成、特点及用法等作一较全面阐述,以帮助同学们掌握这一重要的语法知识。 一、with结构的构成 它是由介词with或without+复合结构构成,复合结构作介词with或without的复合宾语,复合宾语中第一部分宾语由名词或代词充当,第二部分补足语由形容词、副词、介词短语、动词不定式或分词充当,分词可以是现在分词,也可以是过去分词。With结构构成方式如下: 1. with或without-名词/代词+形容词; 2. with或without-名词/代词+副词; 3. with或without-名词/代词+介词短语; 4. with或without-名词/代词+动词不定式; 5. with或without-名词/代词+分词。 下面分别举例: 1、She came into the room,with her nose red because of cold.(with+名词+形容词,作伴随状语) 2、With the meal over ,we all went home.(with+名词+副词,作时间状语)

3、The master was walking up and down with the ruler under his arm。(with+名词+介词短语,作伴随状语。) The teacher entered the classroom with a book in his hand. 4、He lay in the dark empty house,with not a man ,woman or child to say he was kind to me.(with+名词+不定式,作伴随状语) He could not finish it without me to help him.(without+代词+不定式,作条件状语) 5、She fell asleep with the light burning.(with+名词+现在分词,作伴随状语) 6、Without anything left in the cupboard,she went out to get something to eat.(without+代词+过去分词,作为原因状语) 二、with结构的用法 在句子中with结构多数充当状语,表示行为方式,伴随情况、时间、原因或条件(详见上述例句)。 With结构在句中也可以作定语。例如: 1.I like eating the mooncakes with eggs. 2.From space the earth looks like a huge water-covered globe with a few patches of land sticking out above the water. 3.A little boy with two of his front teeth missing ran into the house. 三、with结构的特点 1. with结构由介词with或without+复合结构构成。复合结构中第一部分与第二部分语法上是宾语和宾语补足语关系,而在逻辑上,却具有主谓关系,也就是说,可以用第一部分

With 的用法

With得用法 1.With sb/sthdoing 表主动且进行 2.Withsth being done表被动且进行 3.withsth done表被动且完成 4.with sth todo表示将来 1.从语法角度瞧: with 就是介词,所以后面跟得就是宾语;宾语后面得可以被称为就是宾补。 1.Withoutanyone noticing, Istol e into the room、 With so many children talking and laughing, Icouldn’tsettle down to my work、 2.With so much work beingdone, I can’t spare any minute。 3.With so muchworkdone, Ihad a niceday。 4.With a lot of problems to settle, the newly elected president is having a hardtime。 Lie 说谎-lied-lied—lying Lie躺;存在;位于-lay-lain—lying

Lay 放置;产卵下蛋-laid—laid-laying He lied说谎to me that he hadn't seen the bag that I had laid 放置on the counter、Infact itwaslying存在beside him on the ground。 Hissuggestion aiming(aim) to remov eyourbadhabit is acceptable。 His suggestion aimed(aim) atremoving your bad habit isacceptable. 迎合cater for 做出调整make adjustments 在这之前previous to this 协商negotiate 为…而准备bemeant for/be intendedfor 明年将被开展得建造工程不就是很容易被及时完成、The buildingproject to be carriedoutnext year is not easyto complete. Require doing=need doing = want d oing以主动表被动 All cars requiretesting/to be tested。 Pull through康复;完成十分困难得事情

相关主题
相关文档
最新文档