The relationship between classification of multi-domain proteins using an alignment-free approach and their functions: a case study with immunoglobulins.

Abstract:

:Establishing functional relationships between multi-domain protein sequences is a non-trivial task. Traditionally, delineating functional assignment and relationships of proteins requires domain assignments as a prerequisite. This process is sensitive to alignment quality and domain definitions. In multi-domain proteins due to multiple reasons, the quality of alignments is poor. We report the correspondence between the classification of proteins represented as full-length gene products and their functions. Our approach differs fundamentally from traditional methods in not performing the classification at the level of domains. Our method is based on an alignment free local matching scores (LMS) computation at the amino-acid sequence level followed by hierarchical clustering. As there are no gold standards for full-length protein sequence classification, we resorted to Gene Ontology and domain-architecture based similarity measures to assess our classification. The final clusters obtained using LMS show high functional and domain architectural similarities. Comparison of the current method with alignment based approaches at both domain and full-length protein showed superiority of the LMS scores. Using this method we have recreated objective relationships among different protein kinase sub-families and also classified immunoglobulin containing proteins where sub-family definitions do not exist currently. This method can be applied to any set of protein sequences and hence will be instrumental in analysis of large numbers of full-length protein sequences.

journal_name

Mol Biosyst

journal_title

Molecular bioSystems

authors

Bhaskara RM,Mehrotra P,Rakshambikai R,Gnanavel M,Martin J,Srinivasan N

doi

10.1039/c3mb70443b

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

1082-93

issue

5

eissn

1742-206X

issn

1742-2051

journal_volume

10

pub_type

杂志文章
  • A novel SNP detection technique utilizing a multiple primer extension (MPEX) on a phospholipid polymer-coated surface.

    abstract::Conventional methods for detecting single nucleotide polymorphisms (SNPs), including direct DNA sequencing, pyrosequencing, and melting curve analysis, are to a great extent limited by their requirement for particular detection instruments. To overcome this limitation, we established a novel SNP detection technique ut...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/b701645j

    authors: Imai K,Ogai Y,Nishizawa D,Kasai S,Ikeda K,Koga H

    更新日期:2007-08-01 00:00:00

  • Identification of key active constituents of Buchang Naoxintong capsules with therapeutic effects against ischemic stroke by using an integrative pharmacology-based approach.

    abstract::Integrative pharmacology has been used to identify the key active constituents (KACs) of Buchang Naoxintong capsules (BNCs), a traditional Chinese medical preparation; this approach involves the evaluation of the content profiles and drug-like properties of the BNC constituents and development of an ingredient-target ...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c5mb00460h

    authors: Haiyu X,Yang S,Yanqiong Z,Qiang J,Defeng L,Yi Z,Feng L,Hongjun Y

    更新日期:2016-01-01 00:00:00

  • Thermal unfolding simulations of NBD1 domain variants reveal structural motifs associated with the impaired folding of F508del-CFTR.

    abstract::We employed high-temperature classical molecular dynamics (MD) simulations to investigate the unfolding process of the wild-type (WT) and F508del-NBD1 domains of CFTR protein, with and without second-site mutations. To rationalize the in vitro behavior of F508del-NBD1, namely its lower folding yield and higher aggrega...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c6mb00193a

    authors: Estácio SG,Martiniano HF,Faísca PF

    更新日期:2016-08-16 00:00:00

  • Chemical genetics and cereal starch metabolism: structural basis of the non-covalent and covalent inhibition of barley β-amylase.

    abstract::There are major issues regarding the proposed pathway for starch degradation in germinating cereal grain. Given the commercial importance but genetic intractability of the problem, we have embarked on a program of chemical genetics studies to identify and dissect the pathway and regulation of starch degradation in ger...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c0mb00204f

    authors: Rejzek M,Stevenson CE,Southard AM,Stanley D,Denyer K,Smith AM,Naldrett MJ,Lawson DM,Field RA

    更新日期:2011-03-01 00:00:00

  • Production of indole antibiotics induced by exogenous gene derived from sponge metagenomes.

    abstract::Sponge metagenomes are accessible genetic sources containing genes and gene clusters responsible for the biosynthesis of sponge-derived bioactive natural products. In this study, we obtained the clone pDC112, producing turbomycin A and 2,2-di(3-indolyl)-3-indolone, based on the functional screening of the metagenome l...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c5mb00131e

    authors: Takeshige Y,Egami Y,Wakimoto T,Abe I

    更新日期:2015-05-01 00:00:00

  • BH3 helix-derived biophotonic nanoswitches regulate cytochrome c release in permeabilised cells.

    abstract::Dynamic physical interactions between proteins underpin all key cellular processes and are a highly attractive area for the development of research tools and medicines. Protein-protein interactions frequently involve α-helical structures, but peptides matching the sequences of these structures usually do not fold corr...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c3mb70246d

    authors: Mart RJ,Errington RJ,Watkins CL,Chappell SC,Wiltshire M,Jones AT,Smith PJ,Allemann RK

    更新日期:2013-11-01 00:00:00

  • Identification of potential CCR5 inhibitors through pharmacophore-based virtual screening, molecular dynamics simulation and binding free energy analysis.

    abstract::CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs), plays a vital role in inflammatory responses to infection. Alterations in the expression of CCR5 have been correlated with disease progression in many types of cancers. The idea of using CCR5 as a target for therapeutic intervention has b...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c6mb00577b

    authors: Wang J,Shu M,Wang Y,Hu Y,Wang Y,Luo Y,Lin Z

    更新日期:2016-10-18 00:00:00

  • A view of RNase P.

    abstract::Major progress in the study of RNase P has resulted from crystallography of bacterial catalytic subunits and the discovery of catalytic activity in eukaryotes. Several new substrates have also been identified, primarily in bacteria but also in yeast. Our current world should be called the "RNA-protein world" rather th...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章,评审

    doi:10.1039/b707850c

    authors: Altman S

    更新日期:2007-09-01 00:00:00

  • A novel approach applying a chemical biology strategy in phenotypic screening reveals pathway-selective regulators of histone 3 K27 tri-methylation.

    abstract::Epigenetic regulation by histone methylation is crucial for proper programming of the genome during development. Homeostasis of histone methylation is balanced by the activities of histone methyltransferases and demethylases. Although these methyltransferases and demethylases represent logical targets for potential dr...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c3mb70413k

    authors: Liu Y,Platchek M,Kement B,Bee WT,Truong M,Zeng X,Hung S,Lin H,Morrow D,Kallal LA,Xie Q,Agarwal P,Pope AJ,Wu Z

    更新日期:2014-02-01 00:00:00

  • Base excision DNA repair in the embryonic development of the sea urchin, Strongylocentrotus intermedius.

    abstract::In actively proliferating cells, such as the cells of the developing embryo, DNA repair is crucial for preventing the accumulation of mutations and synchronizing cell division. Sea urchin embryo growth was analyzed and extracts were prepared. The relative activity of DNA polymerase, apurinic/apyrimidinic (AP) endonucl...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c5mb00906e

    authors: Torgasheva NA,Menzorova NI,Sibirtsev YT,Rasskazov VA,Zharkov DO,Nevinsky GA

    更新日期:2016-06-21 00:00:00

  • Multi-well fungal co-culture for de novo metabolite-induction in time-series studies based on untargeted metabolomics.

    abstract::The induction of fungal metabolites by fungal co-cultures grown on solid media was explored using multi-well co-cultures in 2 cm diameter Petri dishes. Fungi were grown in 12-well plates to easily and rapidly obtain the large number of replicates necessary for employing metabolomic approaches. Fungal culture using suc...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c4mb00223g

    authors: Bertrand S,Azzollini A,Schumpp O,Bohni N,Schrenzel J,Monod M,Gindro K,Wolfender JL

    更新日期:2014-07-29 00:00:00

  • Pretubulysin derived probes as novel tools for monitoring the microtubule network via activity-based protein profiling and fluorescence microscopy.

    abstract::Microtubules (mt) are highly dynamic polymers composed of alpha- and beta-tubulin monomers that are present in all dividing and non-dividing cells. A broad variety of natural products exists that are known to interfere with the microtubule network, by either stabilizing or de-stabilizing these rope-like polymers. Amon...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c2mb25144b

    authors: Eirich J,Burkhart JL,Ullrich A,Rudolf GC,Vollmar A,Zahler S,Kazmaier U,Sieber SA

    更新日期:2012-08-01 00:00:00

  • Transcription regulatory networks in Caenorhabditis elegans inferred through reverse-engineering of gene expression profiles constitute biological hypotheses for metazoan development.

    abstract::Differential gene expression governs the development, function and pathology of multicellular organisms. Transcription regulatory networks study differential gene expression at a systems level by mapping the interactions between regulatory proteins and target genes. While microarray transcription profiles are the most...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/B908108a

    authors: Vermeirssen V,Joshi A,Michoel T,Bonnet E,Casneuf T,Van de Peer Y

    更新日期:2009-12-01 00:00:00

  • Design and development of histone deacetylase (HDAC) chemical probes for cell-based profiling.

    abstract::Histone deacetylases (HDACs) contribute to regulation of gene expression by mediating higher-order chromatin structures. They assemble into large multiprotein complexes that regulate activity and specificity. We report the development of small molecule probes with class IIa and pan-HDAC activity that contain photoreac...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c6mb00109b

    authors: Albrow VE,Grimley RL,Clulow J,Rose CR,Sun J,Warmus JS,Tate EW,Jones LH,Storer RI

    更新日期:2016-05-24 00:00:00

  • NTSMDA: prediction of miRNA-disease associations by integrating network topological similarity.

    abstract::Recently, accumulating studies have indicated that microRNAs (miRNAs) play an important role in exploring the pathogenesis of various human diseases at the molecular level and may result in the design of specific tools for diagnosis, treatment evaluation and prevention. Experimental identification of disease-related m...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c6mb00049e

    authors: Sun D,Li A,Feng H,Wang M

    更新日期:2016-06-21 00:00:00

  • An in-depth view of human serum albumin corona on gold nanoparticles.

    abstract::Upon entering biological systems, such as the blood stream, nanoparticles form molecular complexes with the proteins encountered called protein coronas, which shield the surface of the exogenous nanoparticle. The most abundant blood proteins, such as albumin, initially occupy the surface of the nanoparticle. Owing to ...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c4mb00591k

    authors: Ramezani F,Rafii-Tabar H

    更新日期:2015-02-01 00:00:00

  • Non-traditional roles of G protein-coupled receptors in basic cell biology.

    abstract::G protein-coupled receptors (GPCRs) are key signaling proteins that regulate how cells interact with their environment. Traditional signaling cascades involving GPCRs have been well described and are well established and very important clinical targets. With the development of more recent technologies, hints about the...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章,评审

    doi:10.1039/c2mb25429h

    authors: Zhang X,Eggert US

    更新日期:2013-04-05 00:00:00

  • A quantitative high-throughput screen for modulators of IL-6 signaling: a model for interrogating biological networks using chemical libraries.

    abstract::Small molecule modulators are critical for dissecting and understanding signaling pathways at the molecular level. Interleukin 6 (IL-6) is a cytokine that signals via the JAK-STAT pathway and is implicated in cancer and inflammation. To identify modulators of this pathway, we screened a chemical collection against an ...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/b902021g

    authors: Johnson RL,Huang R,Jadhav A,Southall N,Wichterman J,MacArthur R,Xia M,Bi K,Printen J,Austin CP,Inglese J

    更新日期:2009-09-01 00:00:00

  • Studies of N(9)-arenthenyl purines as novel DFG-in and DFG-out dual Src/Abl inhibitors using 3D-QSAR, docking and molecular dynamics simulations.

    abstract::Recently, the development of Src/Abl (c-Src/Bcr-Abl tyrosine kinases) dual inhibitors has attracted considerable attention from the research community for treatment of malignancies. In order to explore the different structural features impacting the Src and Abl inhibitory activities of N(9)-arenethenyl purines and to ...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c4mb00350k

    authors: Ma S,Zeng G,Fang D,Wang J,Wu W,Xie W,Tan S,Zheng K

    更新日期:2015-02-01 00:00:00

  • Acid cleavable PEG-lipids for applications in a ternary gene delivery vector.

    abstract::A novel class of pH-sensitive PEG lipids bearing acid-cleavable acetal linkages and short PEG chains have been synthesised and used in ternary vector formulations. The cleavage pH was influenced by structural components including the terminal PEG moiety and spacer length. ...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/b719782a

    authors: Wong JB,Grosse S,Tabor AB,Hart SL,Hailes HC

    更新日期:2008-06-01 00:00:00

  • PredcircRNA: computational classification of circular RNA from other long non-coding RNA using hybrid features.

    abstract::Recently circular RNA (circularRNA) has been discovered as an increasingly important type of long non-coding RNA (lncRNA), playing an important role in gene regulation, such as functioning as miRNA sponges. So it is very promising to identify circularRNA transcripts from de novo assembled transcripts obtained by high-...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c5mb00214a

    authors: Pan X,Xiong K

    更新日期:2015-08-01 00:00:00

  • A cellular lipidomic study on the Aβ-induced neurotoxicity and neuroprotective effects of EGCG by using UPLC/MS-based glycerolipids profiling and multivariate analysis.

    abstract::The aim of this study was to investigate the cellular lipid metabolism associated with β-amyloid peptide (Aβ)-induced neurotoxicity as well as the neuroprotective effect of (-)-epigallocatechin gallate (EGCG), a major polyphenol in green tea. An ultra-performance liquid chromatography-quadrupole-time-of-flight mass sp...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c2mb25126d

    authors: Zhang H,Wang JR,Yau LF,Ho HM,Chan CL,Hu P,Liu L,Jiang ZH

    更新日期:2012-10-30 00:00:00

  • Efficient Bayesian estimates for discrimination among topologically different systems biology models.

    abstract::A major effort in systems biology is the development of mathematical models that describe complex biological systems at multiple scales and levels of abstraction. Determining the topology-the set of interactions-of a biological system from observations of the system's behavior is an important and difficult problem. He...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c4mb00276h

    authors: Hagen DR,Tidor B

    更新日期:2015-02-01 00:00:00

  • Proteomic analysis of protein adsorption capacity of different haemodialysis membranes.

    abstract::Protein-adsorptive properties are a key feature of membranes used for haemodialysis treatment. Protein adsorption is vital to the biocompatibility of a membrane material and influences membrane's performance. The object of the present study is to investigate membrane biocompatibility by correlating the adsorbed proteo...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c2mb05393d

    authors: Urbani A,Lupisella S,Sirolli V,Bucci S,Amoroso L,Pavone B,Pieroni L,Sacchetta P,Bonomini M

    更新日期:2012-04-01 00:00:00

  • Digital and analogical reality in proteomics investigation.

    abstract::Are protein functions continuous or discretized? Proteomics investigations are starting to address this non-trivial awesome question focusing upon determining the nature of biological molecular relationships. In the following editorial we present a number of experimental studies published in this themed Proteomics Iss...

    journal_title:Molecular bioSystems

    pub_type: 社论

    doi:10.1039/c3mb90013d

    authors: Urbani A,Castagnola M,Fasano M,Bini L,Modesti A,Timperio AM,Roncada P

    更新日期:2013-06-01 00:00:00

  • Structural diversity induced by pyrene intercalators in homogeneous oligodeoxyguanylates.

    abstract::Homogeneous oligodeoxyguanylates incorporating small-molecule intercalator pyrene moieties in a 1,5 relationship form various structures of dimer, trimer, tetramer and internal hairpin form that are yellowish in color because of the intermolecular interactions between the pyrene units. ...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/b926677a

    authors: Jeong HS,Park M,Yi JW,Joo T,Kim BH

    更新日期:2010-06-01 00:00:00

  • Hyperglycemia induced structural and functional changes in human serum albumin of diabetic patients: a physico-chemical study.

    abstract::Structural and functional changes in albumin are of particular interest as numerous studies in vivo have reported a strong involvement of glycated-HSA in the development and progression of chronic diabetic complications. Non-enzymatic addition of glucose molecules to a protein induces structural changes in it. These c...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/c6mb00324a

    authors: Neelofar K,Arif Z,Alam K,Ahmad J

    更新日期:2016-07-19 00:00:00

  • Engineering stochasticity in gene expression.

    abstract::Stochastic fluctuations (noise) in gene expression can cause members of otherwise genetically identical populations to display drastically different phenotypes. An understanding of the sources of noise and the strategies cells employ to function reliably despite noise is proving to be increasingly important in describ...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/b801245h

    authors: Tabor JJ,Bayer TS,Simpson ZB,Levy M,Ellington AD

    更新日期:2008-07-01 00:00:00

  • Fuzziness: linking regulation to protein dynamics.

    abstract::Proteins are dynamic creatures. Intrinsically disordered proteins (IDPs) function as multiplicity of structures and their activities can only be described by stochastic structure-function relationships. In their complex forms, however, IDPs were thought to lose their plasticity and behave similarly to globular protein...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章,评审

    doi:10.1039/c1mb05234a

    authors: Fuxreiter M

    更新日期:2012-01-01 00:00:00

  • Methodology of reversible protein labeling for ratiometric fluorescent measurement.

    abstract::The first fluorescent labeling technology, which can induce not only an increase in the fluorescence intensity but also a shift in the fluorescence spectrum, has been developed for "ratiometric" measurements for a protein by utilizing a newly designed "field-sensitive" fluorescent probe and its corresponding unique am...

    journal_title:Molecular bioSystems

    pub_type: 杂志文章

    doi:10.1039/b515777c

    authors: Soh N,Seto D,Nakano K,Imato T

    更新日期:2006-02-01 00:00:00