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1
Jones, Susan. "Protein-protein interactions." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338952.
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Cooper, Simon T. "PAX6 protein-protein interactions." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/29070.
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The gene PAX6 is located on chromosome 11 (11p13) and encodes a transcription factor (PAX6) that is expressed early in development. The PAX6 protein is expressed in the developing eye, regions of the brain, central nervous system (CNS), nasal epithelium and pancreas. PAX6 is best known for its role eye development with heterozygous mutations causing congenital ocular malformations. However, it must be remembered that PAX6 has multiple functions in the brain including specification of neuronal subtypes and axon guidance. There is growing understanding of the role of PAX6 as a transcription factor during development, and many of its DNA targets have recently been defined. However, almost nothing is known about the proteins with which PAX6 interacts. In the initial stage of my research I identified a conserved region consisting of the final 32 amino acids of the PST (proline, serine and threonine rich) domain of PAX6. Based on sequence homology and secondary structure predictions I classed this region as a novel domain, the ‘C terminal domain’. Next I used the yeast 2-hybrid system to investigate possible PAX6 protein interactions. By screening a mouse brain cDNA library with the C terminal domain and whole PST domain, I identified three novel and interesting interactors, HOMER3, DNCL1 and TRIM11. I re-confirmed these interactions in a pairwise manner using the yeast 2-hybrid system, and I showed that the C terminal domain was vital for the interactions between PAX6 and HOMER3 or DNCL1. Furthermore, certain C terminal mutations that are known to cause ocular malformations in patients are also sufficient to reduce or abolish these interactions. I attempted to further characterise the interactions by co-immunoprecipitation. However, this was not possible due to technical difficulties.
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Braute, Petter, and Jorg Eliassen Rødsjø. "Protein function prediction using annotated protein-protein interaction networks." Thesis, Norwegian University of Science and Technology, Department of Computer and Information Science, 2005. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-9177.
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Govers-Riemslag, Josepha Wilhelmina Philomena. "Protein-protein and protein-membrane interactions in prothrombin activation." Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1994. http://arno.unimaas.nl/show.cgi?fid=6949.
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Lendel, Christofer. "Molecular principles of protein stability and protein-protein interactions." Doctoral thesis, Stockholm, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-480.
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Kneissl, Sabine. "Photocontrol of protein-protein and protein-nucleic acid interactions." Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/54835/.
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Proteins often depend on a-helices for binding to other biomacromolecules. Reversible control of a-helix stability was accomplished in previous studies by incorporating a photoisomerisable azobenzene cross-linker into peptides, subsequently enabling the optical control of DNA-protein interactions. This approach was extended in this study to include protein-protein and protein-RNA interactions. One of the primary regulatory components in apoptosis signalling is the antiapoptotic protein Bcl-xL which interacts with the a-helical BH3 domain of the Bak protein. The Rev/RRE interaction is crucially involved in the life cycle of Human Immunodeficiency Virus. These interactions were targeted by designing peptides based on the BH3 domain of Bak and on the RNA-binding domain of Rev these peptides are activated by external light pulses after the incorporation of the cross-linker. The ability to control cross-linker conformation and hence peptide secondary structure was demonstrated by CD and UV/Vis spectroscopy. The binding to the target structure and complex disruption was determined in the dark-adapted and irradiated states using fluorescence based assays. Structural studies using NMR spectroscopy demonstrated that the alkylated peptides bind to the same part of the target molecule as the wild-type peptide, regardless of their structure. Moreover, one of the BH3 domain-based peptides and the light-controllable transcription factor PhotoMyoD were modified with protein transduction domains to enable future in vivo studies. Overall, this work opens the possibility to interfere reversibly and specifically with protein-protein and protein-RNA interactions and to study and modulate cellular function by optical control.
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Moont, Gidon. "Computational modelling of protein/protein and protein/DNA docking." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445703/.
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The docking problem is to start with unbound conformations for the components of a complex, and computationally model a near-native structure for the complex. This thesis describes work in developing computer programs to tackle both protein/protein and protein/DNA docking. Empirical pair potential functions are generated from datasets of residue/residue interactions. A scoring function was parameterised and then used to screen possible complexes, generated by the global search computer algorithm FTDOCK using shape complementarity and electrostatics, for 9 systems. A correct docking (RMSD < 2.5A) is placed within the top 12% of the pair potential score ranked complexes for all systems. The computer software FTDOCK is modified for the docking of proteins to DNA, starting from the unbound protein and DNA coordinates modelled computationally. Complexes are then ranked by protein/DNA pair potentials derived from a database of 20 protein/DNA complexes. A correct docking (at least 65% of correct contacts) was identified at rank < 4 for 3 of the 8 complexes. This improved to 4 out of 8 when the complexes were filtered using experimental data defining the DNA footprint. The FTDOCK program was rewritten, and improved pair potential functions were developed from a set of non-homologous protein/protein interfaces. The algorithms were tested on a non-homologous set of 18 protein/protein complexes, starting with unbound conformations. Us ing cross-validated pair potential functions and the energy rninimisation software MultiDock, a correct docking ( RMSD of CQ interface 25% correct contacts) is found in the top 10 ranks in 6 out of 18 systems. The current best computational docking algorithms are discussed, and strategies for improvement are suggested.
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Chen, Dan. "Regulation of protein kinase C by protein-protein interactions /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3112821.
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Ginn, C. L. "Protein PEGylation on protein folding." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1403227/.
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E.coli is one of the most widely utilised hosts for protein expression due to its rapid growth, low production costs and high product yields. Often proteins are deposited as insoluble inclusion bodies that later require refolding to achieve biological activity. As a result of misfolding and aggregation for many proteins refolding is the yield limiting step in their production. Relevant therapeutic proteins obtained from E.coli include the α-helical barrel proteins (e.g. interferon-α2). Many proteins derived from E.coli are further modified after refolding by the covalent conjugation of poly(ethylene glycol) (PEG). This is known as PEGylation and several PEGylated α-helical barrel proteins are now routinely used in the clinic. PEGylation is used to address the short circulation half-life, immunogenicity and poor stability associated with many protein-based therapeutics. Our method of PEGylation is site specific. Conjugation occurs by bis-alkylation and takes advantage of the presence of the two free thiols from native disulfide bonds that have been reduced. The conjugated product has PEG linked to the protein through a three-carbon bridge spanning the two thiols derived from the native disulfide. Currently proteins are first purified and then a PEG reagent is used to covalently conjugate PEG to the protein. The PEG-protein conjugate is then purified. This means the protein has to be purified twice which can reduce yields. PEGylating the protein during its initial refolding would avoid the need of two downstream purification processes resulting in a more efficient process with an improved product yield. Therefore the aim of this project is to integrate the process of protein folding and PEGylation to make the production of PEGylated proteins more economically viable allowing their widespread use in the clinic. In this project the following hypotheses will be tested i) Reducing the number of purification steps that need to be performed to improve the overall yield of recovered protein, ii) The ability of PEG to impart the properties of a glycosyl group or a chaperone and protect the protein against aggregation during the folding process, iii) our method of PEGylation in particular should promote the formation of the protein’s disulfides bond and therefore the protein’s thermodynamically stable native state and iv) that the specificity of the conjugation can still be maintained despite the exposure of more sites of conjugation. Here we examine this process with different model alpha helical barrel proteins namely leptin, IFN-β and EPO. In each case the protein was denatured and fully reduced then refolded in the presence of a thiol specific, bis-alkylation PEG reagent allowing us to effectively capture the cysteine thiols during the refolding process. For IFN-β which is highly prone to aggregation, refolding yields in the presence of the PEG reagent were much improved suggesting that our method of PEGylation had a stabilising effect on the protein structure during refolding. This improved stability was also found to benefit the protein after PEGylation. Isolation of the purified PEGylated IFN- conjugate could be achieved in a single purification step in good yield. A similar activity to that generated on PEGylation of the fully folded protein was observed suggesting that for a protein with an accessible disulfide PEGylation did not significantly affect its folding. Some work was also carried out on RNase A and T1 which contain multiple inaccessible disulfides. In this instance PEGylation appeared to hinder the refolding process either by sterically hindering the formation of the protein’s native structure or by incorrect disulfide bond formation. The work described herein therefore suggests that it is possible to refold and PEGylate proteins within a single step but the effectiveness of this approach is likely to be protein dependant.
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McDowall, Mark. "Human protein-protein interaction prediction." Thesis, University of Dundee, 2011. https://discovery.dundee.ac.uk/en/studentTheses/697e465a-edbd-41d2-acda-5910a49e4157.
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Protein-protein interactions are essential for the survival of all living cells, allowing for processes such as cell signalling, metabolism and cell division to occur. Yet in humans there are only >38k annotated interactions of an interactome estimated to range between 150k to 600k interactions and out of a potential 300M protein pairs.Experimental methods to define the human interactome generate high quality results, but are expensive and slow. Computational methods play an important role to fill the gap.To further this goal, the prediction of human protein-protein interactions was investigated by the development of new predictive modules and the analysis of diverse datasets within the framework of the previously established PIPs protein-protein interaction predictor Scott and Barton 2007. New features considered include the semantic similarity of Gene Ontology annotating terms, clustering of interaction networks, primary sequences and gene co-expression. Integrating the new features in a naive Bayesian manner as part of the PIPs 2 predictor resulted in two sets of predictions. With a conservative threshold, the union of both sets is >300k predicted human interactions with an intersect of >94k interactions, of which a subset have been experimentally validated. The PIPs 2 predictor is also capable of making predictions in organisms that have no annotated interactions. This is achieved by training the PIPs 2 predictor based on a set of evidence and annotated interactions in another organism resulting in a ranking of protein pairs in the original organism of interest. Such an approach allows for predictions to be made across the whole proteome of poorly characterised organism, rather than being limited only to proteins with known orthologues. The work described here has increased the coverage of the human interactome and introduced a method to predict interactions in organisms that have previously had limited or no annotated interactions. The thesis aims to provide a stepping stone towards the completion of the human interactome and a way of predicting interactions in organisms that have been less well studied, but are often clinically relevant.
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Ospina, Forero Luis Eduardo. "Modelling protein-protein interaction networks." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:c5150074-e160-4c59-8c23-f8804ae3dd2e.
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Proteins, the main motors of the cell, are in charge of performing a diverse array of biological functions. They rarely perform those functions alone, but generally work as groups of proteins that through a complex array of interactions perform a single biological function. These complex interactions between different proteins are often analysed via network theory, where a protein-protein interaction (PPI) network is created considering each protein as a node and each of their interactions as edges. Different approaches from the perspective of network analysis have been proposed to describe, analyse, and predict PPI networks. Some methods focus on the use of network summary statistics, community detection, random graph models, and machine learning procedures. However, despite the large effort invested in PPI network research, current models fail to describe well the structure of PPI networks. Small overrepresented subgraphs, which have been thought as the building blocks of networks, have been shown to be important patterns in gene regulatory networks, and there is evidence that suggests they may be evolutionarily conserved across the PPI networks of different organisms. Hence, a first step to better understand the structure of protein-protein interaction networks, is to describe how the local structure of these networks, accounted by the occurrence of small connected subgraphs, is created. We approach this problem in two stages. In the first stage, we provide a framework to statistically assess if a random graph model can describe the occurrence of different small connected subgraphs observed in PPI networks. Then, by applying this framework we find that state-of-the-art network comparison methods based on subgraph counts struggle at finding similarities between networks that have different numbers of nodes or edges. Hence, in joint work with Dr. Anatol Wegner, Dr. Robert Gaunt, Professor Gesine Reinert, and Professor Charlotte M. Deane, we propose a novel network comparison method, NetEmd, that tackles this problem indirectly by proposing a method that is invariant to translations and rescalings of subgraph count distributions, and which is better able to detect similarities across networks with different number of nodes or edges. In the second stage, we use NetEmd, along with three other state-of-the-art network comparison methods, to test the ability of several random graph models to describe the occurrence of subgraphs counts in the PPI networks of six organisms, and in multiple smaller sections of these networks. We find that the overall occurrence of small connected subgraphs could potentially be described by two network generation mechanisms operating in complementary sections of the PPI networks. In addition we find that cellular compartment-specific PPI networks can be potentially described by a single model that captures, with only two parameters, both, the common properties between the different cellular compartment networks, and their individual structural features.
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Herrington-Symes, A. P. "Protein-protein conjugation using interferon." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1464509/.
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Therapeutic proteins are often potent and have rapid onsets of action. Unfortunately protein-based medicines can be immunogenic and have short half-lives. The circulation half-life of many proteins has been improved by the covalent conjugation of poly(ethylene)glycol (PEG) to the protein. For example, PEGylated interferon-2 (PEGASYS® and PEG-INTRON®) has become a first line treatment for hepatitis C. The aim of this thesis was to examine the possibility of using a homobifunctional PEG reagent to make protein dimers. Our group has developed PEGylation reagents that undergo conjugation by bis-alkylation to selectively conjugate either (i) two cysteine thiols from a native disulfide or (ii) two histidine residues in a polyhistidine tag. It was hypothesised that IFN dimers (IFN-PEG-IFN) could be prepared with higher retained activity than monoPEGylated IFN. It was also hypothesised that a heterodimer of IFN and an antibody fragment (Fab) could be made while retaining the activity of both proteins within the heterodimer. His8IFN-PEG-His8IFN and IFN-PEG-IFN homodimers were prepared by site-selective conjugation to the N-terminal 8-polyhistidine tag and to one of the disulfides of IFN respectively. These homodimer conjugates were characterised in terms of purity and in vitro activity. The in vitro cell based assays were optimised to accurately elucidate the specific activities of the IFN conjugates. The His8IFN-PEG20-His8IFN homodimer was found to retain greater activity than IFN-PEG20-IFN. The increased activity was thought to be due to conjugation to the polyhistidine tag, which is distal from the IFN binding surface. It was also found that IFN-PEG10-IFN homodimer retained greater activity than PEG10-IFN, which could be due to the presence of the second IFN molecule in the IFN-PEG10-IFN homodimer. Two different Fabs were used to prepare the IFN-PEG-Fab heterodimers. Conjugation was conducted at one disulfide of IFN and the accessible interchain disulfide of the Fab. One Fab was derived from a polyclonal antibody to albumin (Fabalb) and the rationale for this heterodimer was that a longer lasting form of IFN could be made (IFN-PEG20-Fabalb). The other Fab was derived from bevacizumab (Fabbeva) to give an IFN-PEG20-Fabbeva heterodimer that could, in principle, display antiangiogenic properties. Both heterodimers were evaluated using antiviral and antiproliferative assays to determine the activity of IFN in the conjugate. The IFN-PEG20-Fabalb conjugate displayed a 10-fold reduction in activity compared to IFN-PEG20-Fabbeva. It was thought that Fabalb underwent competitive binding with components of the media. Interestingly, the IFN-PEG20-Fabbeva heterodimer displayed greater activity than PEG20-IFN and IFN-PEG20-IFN in both the antiviral and antiproliferative assays. The binding properties of Fabbeva were determined by SPR. It was observed that the dissociation rate of IFN-PEG20-Fabbeva was similar to Fabbeva and PEG20-Fabbeva. IFN-PEG20-Fabalb was found to have a similar dissociation rate to Fabalb. However, PEG20-Fabalb was found to have a slower dissociation to both IFN-PEG20-Fabalb and Fabalb, this result requires further investigation but was thought to be due to the sample impurity. The association rates of heterodimers were found to similar to the PEG-Fab conjugates but slower than their native Fabs. This data suggests that the novel IFN-PEG20-Fabbeva and IFN-PEG20-Fabalb heterodimer conjugates have retained their binding affinities to their antigens. Overall, it was shown that a homobifunctional bis-alkylating conjugation reagent (e.g. PEG di(bis)sulfone 4) could be used successfully to prepare dimeric protein conjugates. This work highlighted the importance to ensure the homobifunctional conjugation reagent was pure, especially for the preparation of protein heterodimeric conjugates. To develop this work further, it would be important to investigate three broad areas: i) improving the purity of the starting homobifunctional reagents, ii) evaluate the in vivo efficacy of the resulting protein homo-/hetero-dimers and iii) determine the overall potential for efficient scaling of the process to make the desired protein homo-/hetero-dimers.
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Schnee, Margit. "Protein fragment complementation assay for studying viral protein-protein interactions." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-65582.
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Ruan, Peiying. "Computational Methods for Analyzing Protein Complexes and Protein-Protein Interactions." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/199433.
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Stevenson, Calum. "Database mining studies on protein-peptide and protein-protein interactions." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/7644.
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A major area of interest is the identification of proteins that play a role in hormone dependent cancers and in collaboration with the MRC Centre for Reproductive Health we studied the gonadotropin releasing hormone receptor (GnRH-R). Other targets described in the thesis are the SH3 domain of PSD-95 and the protein BLyS. In order to identify potential inhibitory small molecules we have used a variety of computational data base mining approaches as well as using and developing experimental binding assays. It has become increasingly challenging to evaluate the most representative drug like small molecule compounds when using traditional high throughput screening methods. This thesis assesses the use of in silico tools to probe key protein-protein and protein-peptide interactions. These tools provide a means to identify enriched compound datasets which can be purchased and tested in vitro in a time and cost efficient way. The transmembrane protein GnRH-R provides an interesting opportunity to identify small molecules that could inhibit the binding of its peptide ligand GnRH. This is a challenging project as there are few examples in the literature of drug-like molecules that bind to such protein-peptide interfaces. The first step involved receptor modelling using solved crystal structures of homologous proteins. The model was then validated by developing structure activity relationships for established high affinity ligands. We also performed crystallographic and biophysical studies on the native GnRH decapeptide. Two other protein-protein systems were also examined using the same virtual screening and experimental ligand binding methodology. SH3 domains play an important role in cell signalling and we used the PSD-95 protein as our target for study as a crystal structure has been published. As well as identifying potential ligands we characterised structural properties of PSD-95 fusion proteins and also developed the basis for compound assay. The third system studied was B Lymphocyte Stimulator (BLyS) which is a target for treatment of a number of autoimmune diseases. This presented an interesting target for study as the protein binds to multiple receptors depending on its multimeric state. BLyS protein was characterised using electron microscopy and other biophysical techniques.
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Chiang, Angela Hsieh Fu-hung. "Protein-protein interaction of soy protein isolate from extrusion processing." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/5099.
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Thesis (M.S.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on May 11, 2009) Thesis advisor: Fu-Hung Hsieh. Includes bibliographical references.
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Cao, Zehui. "Designer oligonucleotides for probing dna-protein and protein-protein interactions." [Gainesville, Fla.] : University of Florida, 2004. http://purl.fcla.edu/fcla/etd/UFE0008333.
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Chen, Kai. "Use of green fluorescent protein for the analysis of protein-protein and protein-DNA interactions." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/4886.
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Restriction modification (RM) systems play a crucial role in preventing the entry of foreign DNA into the bacterial cell. The best studied Type I RM system is EcoKI from Escherichia coli K12. Both bacteriophage and conjugative plasmids have developed a variety of strategies to circumvent the host RM system. One such strategy involves the production of antirestriction proteins that mimic a short segment of DNA and efficiently inhibit the RM system. The main aim of this project was to analyse the interaction of EcoKI and its cognate methylase (MTase) with the T7 antirestriction protein, known as overcome classical restriction (Ocr), and various ArdA antirestriction proteins. Currently, there is a paucity of structural data on the complex formed between the Type I system and the antirestriction proteins. The aim of this work was twofold; (i) compare the interaction of MTase with DNA and Ocr and (ii) quantify the strength of interaction between MTase and various ArdA proteins. The MTase was fused to the Green Fluorescent Protein (GFP) to facilitate determination of the orientation of interaction with DNA and Ocr. Time resolved fluorescence measurements were carried out using the GFP-MTase fusion to determine the fluorescence lifetime and anisotropy decay. These experiments were conducted using a time resolved fluorescence instrument fabricated in-house. The values determined in these experiments were then used to perform fluorescence resonance energy transfer (FRET) measurements with fluorescently labelled DNA or Ocr. These measurements gave information concerning the relative orientation of the MTase with either DNA or Ocr. The GFP-MTase fusion was also used to quantify the strength of interaction with various ArdA proteins. Previous attempts to determine the strength of interaction between MTase and ArdA proteins by employing conventional techniques have been unsuccessful. Therefore, a novel method was developed that exploits the interaction of MTase with a cation exchange medium, which can subsequently be displaced upon binding to ArdA. This method facilitated the determination, for the first time, of a set of binding affinities for the MTase and ArdA interaction.
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Chen, Huiling Zhou Huan Xiang Ferrone Frank A. "Prediction of protein structures and protein-protein interactions : a bioinformatics approach /." Philadelphia, Pa. : Drexel University, 2005. http://dspace.library.drexel.edu/handle/1860/481.
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Kulis, Michael D. "Islet neogenesis associated protein-related protein from gene to folded protein /." Available online, Georgia Institute of Technology, 2006, 2006. http://etd.gatech.edu/theses/available/etd-01112006-195113/.
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Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2006.Shuker, Suzanne, Committee Chair ; Doyle, Donald, Committee Member ; Orville, Allen, Committee Member ; Barry, Bridgette, Committee Member ; McCarty, Nael, Committee Member.
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Kulis, Michael D. Jr. "Islet Neogenesis Associated Protein-Related Protein: From Gene to Folded Protein." Diss., Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/10436.
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Type 1 diabetes is the direct result of an autoimmune attack on the pancreatic islet cells. The islets contain b cells, which are the only type of cell capable of supplying insulin in the human body. The destruction of these cells leaves the diabetic to rely on exogenous insulin to maintain a normal blood sugar level. Insulin therapy allows the diabetic to deal with the symptoms of the disease, but does nothing for the underlying condition. In order to truly cure the disease, the strategy is to replenish the b cells in the diabetic. Islet neogenesis associated protein (INGAP) has been shown to regenerate islet cells and reverse experimentally-induced diabetes in animal models. The INGAP pentadecapeptide is a 15 amino acid peptide from INGAP with comparable activity to the full-length protein. This 15-mer is undergoing clinical trials for treating diabetes.
The overall goal of the project described in this work is to determine the structure of the INGAP pentadecapeptide for use in structure-based drug design of non-peptide mimics of the 15-mer. The first set of experiments in the present work directly examined the 15-mer in solution using NMR. No stable structure of the small peptide was found. The second set of experiments involved a homolog of INGAP, called INGAP-related protein, or INGAPrP. INGAPrP was recombinantly produced in E. coli and subsequently purified and refolded. Refolding of INGAPrP was verified by a 1H-15N HSQC experiment. CD experiments supported the NMR study, indicating helical content in INGAPrP. The folded nature of the protein will allow for the three-dimensional structure of INGAPrP to be determined. The protein structure will show the fold of the 15-mer within the full-length protein. This information will be valuable for the ultimate goal of producing structural mimics of the INGAP pentadecapeptide. Non-peptide mimics should have better oral bioavailability and longer half-lives in vivo.
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Worthington, Andrew Schuyler. "Chemoenzymatic investigations of protein-protein interactions in carrier protein-mediated biosynthesis." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3338769.
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Thesis (Ph. D.)--University of California, San Diego, 2008.Title from first page of PDF file (viewed January 9, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Mohr, Andrea. "Protein-Protein-Interaktionen des G-CSFR." [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=960605398.
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Xia, Zebin. "Peptidomimetics to mimic protein-protein interactions." Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/2239.
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Quenched Molecular Dynamics (QMD) used to explore molecular conformations was developed to operate in Insight II platform for two simulation engines: CHARMm and Discover. Two scripts and procedures were written for molecular minimization, dynamics, minimization of each of several hundred conformers, and cut off. Experience with Insight II/Discover versus Quanta/CHARMm, and between Insight II/CHARMm versus Quanta/CHARMm has taught that the forcefield is the key factor in QMD studies. Protein A has been used for the purification of commercial antibodies, but it is expensive. Seven peptidomimetics of protein A were designed based on the hot-spots located at the helix-loop-helix region of protein A, and synthesized via solid phase using the Fmoc approach. These peptidomimetics were characterized by MS and NMR. The conformations of four peptidomimetics were studied by NMR and CD in water/hexafluoroisopropanol (pH 4). The CD and NMR data show that addition of hexafluoroisopropanol stabilizes their a-helical conformations. The structures of these peptidomimetics in solution were generated with Quanta/CHARMm using NMR data as limits for the QMD technique. Protein G has also been used to purify antibodies, but it is expensive too. A number of protein G mimics were designed as trivalent molecules. An efficient preparation of trivalent molecules having a useful primary amine arm has been developed through solid phase synthesis. The cheap, commercially available poly(propylene imine) dendrimers were used as scaffolds which allow multimerization of functionalized compounds. A small library of trivalent compounds were synthesized using this approach. A portion of compounds in this library were tested by Amersham Biosciences. The seven amino acid modified DAB-Am-4 exhibits strong binding to the IgG/Fab, and is a potential ligand for IgG purification. The interactions between neurotrophins (ie NGF and NT-3) and their receptors are typical drug targets. Fourteen second-generation peptidomimetics showing NGF-like or NT3-like activities in a preliminary bioassay, were resynthesized and tested again. Preliminary and retested data were compared. To access a direct binding assay, five fluorescently labeled peptidomimetics 41a-e were synthesized for a fluorescence activated cell sorting (FACScan) assay. Six monomeric precursors 42 and 43 were prepared on large scales for the library of bivalent turn analogs
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Bateman, Katherine Sophie. "Structural studies of protein, protein interactions." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0020/NQ46804.pdf.
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Laidlaw, Stephen Mark. "Protein-protein interactions of fowlpox virus." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424671.
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Bougouffa, Salim. "Empirical modelling of protein-protein interactions." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529241.
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Robinson, Ross Alexander. "Structural biology of protein - protein interactions." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504517.
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Taylor, M. J. "Protein engineering of staphylococcal protein A." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373965.
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Gill, Katrina Louise. "Protein-protein interactions in membrane proteins." Thesis, University of Newcastle Upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400016.
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Hubbard, Simon Jeremy. "Analysis of protein-protein molecular recognition." Thesis, University College London (University of London), 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360151.
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Richter, Carsten Detlev. "Protein-protein interactions in modular megasynthases." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612738.
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Moal, I. H. "Predicting and characterising protein-protein complexes." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1333249/.
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Macromolecular interactions play a key role in all life processes. The construction and annotation of protein interaction networks is pivotal for the understanding of these processes, and how their perturbation leads to disease. However the extent of the human interactome and the limitations of the experimental techniques which can be brought to bear upon it necessitate theoretical approaches. Presented here are computational investigations into the interactions between biological macromolecules, focusing on the structural prediction of interactions, docking, and their kinetic and thermodynamic characterisation via empirical functions. Firstly, the use of normal modes in docking is investigated. Vibrational analysis of proteins are shown to indicate the motions which proteins are intrinsically disposed to undertake, and the use of this information to model flexible deformations upon protein-protein binding is evaluated. Subsequently SwarmDock, a docking algorithm which models flexibility as a linear combination of normal modes, is presented and benchmarked on a wide variety of test cases. This algorithm utilises state of the art energy functions and metaheuristics to navigate the free energy landscape. Information derived from Langevin dynamics simulations of encounter complex formation in the crowded cytosolic environment can be incorporated into SwarmDock and enhances its performance. Finally, a benchmark of binding free energies derived from the literature is presented. For this benchmark, a large number of molecular descriptors are derived. Machine learning methods are then applied to these in order to derive empirical binding free energy, association rate and dissociation rate functions which take account of the conformational changes which occur upon complexation.
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Agius, R. "Understanding stability of protein-protein complexes." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1462393/.
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For all living organisms, macromolecular interactions facilitate most of their natural functions. Alterations to macromolecular structures through mutations, can affect the stability of their interactions, which may lead to unfavourable phenotypes and disease. Presented here, are a number of computational methods aimed at uncovering the principles behind complex stability - as described by binding affinity and dissociation rate constants. Several factors are known to govern the stability of protein-protein interactions, however, no one factor dominates, and it is the synergistic effect of a number of contributions, which amount to the affinity, and stability of a complex. The characterization of complex stability can thus be presented as a two-fold problem; modelling the individual factors and modelling the synergistic effect of the combination of such individual factors. Using machine learning as a central framework, empirical functions are designed for estimating affinity, dissociation rates and the effects of mutations on these properties. The performance of all models is in turn benchmarked on experimental data available from the literature and carefully curated datasets. Firstly, a wild-type binding free energy prediction model is designed, composed of a diverse set of stability descriptors, which account for flexibility and conformational changes undergone by the complex in question. Similarly, models for estimating the effects of mutations on binding affinity are also designed and benchmarked in a community-wide blind trial. Emphasis here is on the detection of a small subset of mutations that are able to enhance the stability of two de novo protein drugs targeting the flu virus hemagglutinin. Probing further the determinants of stability, a set of descriptors that link hotspot residues with the off-rate of a complex are designed, and applied to models predicting changes in off-rate upon mutation. Finally, the relationship between the distribution of hotspots at protein interfaces, and the rate of dissociation of such interfaces, is investigated.
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Sammond, Deanne Wallander Kuhlman Brian A. "Computational redesign of protein-protein interactions." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,1822.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2008.Title from electronic title page (viewed Dec. 11, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biochemistry and Biophysics Program in Molecular and Cellular Biophysics." Discipline: Biochemistry and Biophysics; Department/School: Medicine.
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Marín, López Manuel Alejandro 1987. "On the development of computational tools for the study of protein-protein interactions and protein-protein binding." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/565599.
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Proteins are involved in almost all cell processes, with physical interaction between them being key to their function and dictated by its 3D structure. Hence, the study of protein-protein interactions and protein-protein binding is crucial to fully understand biological systems. In this thesis, we present V-D2OCK, a fast and accurate data-driven docking tool for high throughput prediction of the structure of protein complexes. We have also studied the conformational space of potential encounter complexes by means of non-specific decoys obtained by docking in order to develop BADock, an accurate binding affinity predictor from the unbound individual structures. Finally, we have published online an integrated and centralized resource (InteractoMIX) that allows to the research community an easy access to a compendium of bioinformatic web applications to study protein-protein interactions.Les proteïnes estan implicades en gairebé tots els processos cel·lulars, amb la interacció física entre elles clau per la seva funció i dictada per la seva estructura 3D. Per tant, l’estudi de la unió i les interaccions proteïna-proteïna és crucial per entendre completament els sistemes biològics. En aquesta tesi, es presenta V-D2OCK, una eina de “docking” dirigit ràpida i precisa per predir l’estructura de complexes de proteïnes a gran escala. També hem estudiat l’espai conformacional de possibles complexes transitoris per mitjà de resultats de “docking” no específics per tal de desenvolupar BADock, un predictor d’energia d’unió a partir de les estructures individuals per separat. Finalment, hem publicat online un recurs integrat i centralitzat (InteractoMIX) que permet a la comunitat investigadora l’accés fàcil a un conjunt de aplicacions web de bioinformàtica per l’estudi de interaccions proteïna-proteïna.
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Rupp, Bernd. "Molecular-Modelling-Untersuchungen zu Wechselwirkungen in Protein-Protein- und Protein-Ligand-Komplexen." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971538522.
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Chin-Sang, Ian D. "Protein-protein interactions and protein phosphatase activity in Caenorhabditis elegans sex determination." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ35125.pdf.
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Albertoni, Barbara [Verfasser]. "Biophysical analysis of protein-protein and protein-small molecule interactions / Barbara Albertoni." Bonn : Universitäts- und Landesbibliothek Bonn, 2011. http://d-nb.info/1044846909/34.
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Cai, Bingjing. "Machine learning approaches for extracting protein complexes from protein-protein interaction networks." Thesis, Ulster University, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603536.
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Recent advances in molecular biology have led to the accumulation of large amounts of data on Protein-Protein Interaction (PPI) networks in different species, such as yeast and humans. Due to the inherent complexity, analysing such volumes of data to extract knowledge, such as protein complexes or regulatory pathways, represents not only an enormous challenge but also a great opportunity. This Thesis explores the application of machine learning approaches to detecting protein complexes from PPI networks obtained by Tandem Affinity Purification/Mass Spectrometry (TAP-MS) experiments. TAP-MS PPI networks are usually constructed as binary, and the co-complex relations are largely ignored. In order to take into account the non-binary information of co-complex relations in T AP-MS PPI networks, a new framework for detecting protein complexes has been proposed. Under this framework, two types of graph clustering algorithms and an integrative evaluation platform combining data-driven and knowledge-based quality measures have been proposed and studied. One type of the proposed graph clustering algorithms is random walk based graph clustering, resulting in Enhanced Random Walk with Restart (ERWR) and Random Walk with Restarting Baits (RWRB). The other type is based on the modelling of TAP-MS PPI networks as bipartite graphs, resulting in the Bipartite Graph based Clustering Algorithm (BGCA). The ER WR algorithm has been developed from the Random Walk with Restart (R WR). The key contribution of the ERWR is the introduction of a tuning factor into the random walk process. The tuning factor strengthens connections between nodes that are closer and weakens those that are distant, so that the random walker prefers moving to nodes which are potentially in the same clusters with the starting node.
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Bennett, Matthew Stuart. "Crystallography of biomolecular complexes, revealing protein-nucleoside, protein-protein acid-drug interactions." Thesis, King's College London (University of London), 2002. https://kclpure.kcl.ac.uk/portal/en/theses/crystallography-of-biomolecular-complexes-revealing-proteinnucleoside-proteinprotein-aciddrug-interactions(4a85b5cd-8a9a-4969-bee3-95fbe46e4257).html.
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Fernández, Suárez Marta. "New reporters of protein trafficking and protein-protein interactions in live cells." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/44678.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2008.Vita.
Includes bibliographical references.
Here, we describe our attempts to harness the exquisite specificity of natural protein and RNA enzymes to develop improved methods to study protein localization and protein-protein interactions in live cells. We first attempted to detect endogenous protein-protein interactions (PPIs) in live cells by means of a ribozyme complementation assay, but we found that the strategy was limited by the interaction affinity constraints and by low ribozyme activity in cells. We then sought to still detect interactions among endogenous proteins but in fixed cells. We devised an improved immunofluorescence (IF) technique, in which the antibodies are conjugated to an enzyme-substrate pair. We chose E. coli biotin ligase (BirA), which catalyzes the covalent ligation of biotin to a 15amino acid recognition sequence (AP). Only upon PPI would BirA be in close enough proximity to biotinylate the AP. Although the use of proximity biotinylation within the IF scheme proved challenging because of the geometric rigidity of the antibody conjugates, we later successfully applied the concept to the study of recombinant proteins in live cells, where BirA and AP were each genetically fused to the proteins of interest. We demonstrated that this method offers a combination of high spatial and temporal resolution with a low rate of false positives. We engineered the BirA/AP affinity to reduce background and eliminate false positives, while still allowing robust detection of relatively transient PPIs (half-life > 1 minute). We demonstrated that the methodology exhibits high specificity for the detection of PPIs in living mammalian cells, with a fold induction in the detected signal upon PPI of - 5-25. Using FRB-FKBP12 system as a model, the BirA/AP(-3) pair was also able to quantitatively predict interaction KIds.
(cont.) Importantly, we showed that proximity biotinylation can detect the subcellular localization of the PPI under study. We also developed a new method for site-specific labeling of proteins in live cells. Through rational design, we re-directed E. coli lipoic acid ligase (LplA) to specifically ligate an unnatural alkyl azide substrate to an engineered 22-amino acid LplA acceptor peptide (LAP) tag. The alkyl azide can then be selectively derivatized with a cyclooctyne conjugated to any probe of interest. We first demonstrated that LplA can be used to label LAP-tagged proteins with Cy3, AlexaFluor568, and biotin at the surface of living mammalian cells, and we then applied the methodology to one- and two-color cellsurface receptor labeling. Finally, we also showed that LplA can site-specifically label intracellular proteins, although the signal/background ratio still needs to be improved.
by Marta Fernández Suárez.
Ph.D.
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Gwynne, Peter John. "Protein-protein interactions of the cold shock protein CspE of Salmonella typhimurium." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/10048.
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Despite their name, a number of the cold shock proteins are expressed during normal growth, and not just during cold shock, in several species. The function of these constitutively expressed CspA paralogues is unclear. In Salmonella Typhimurium (a major worldwide cause of gastrointestinal disease) they have been linked to various stress responses and the establishment of virulence. Study of the cold shock proteins as gene regulators is therefore of great interest, and they also have potential as targets for antimicrobial development. CspE in Salmonella Typhimurium is constitutively expressed during normal growth. In order to determine its function, attempts were made to identify the interactions it forms with other cellular proteins. Initially, a proteomic investigation attempted to identify proteins which complex with CspE by in vivo cross-linking and affinity purification followed by mass spectrometry. Although no defined complex was consistently identified, the results suggested a handful of proteins which might interact with CspE in a weak or transient manner. These proteins included many from the nucleoid and ribosomal entry site, hinting at CspE’s cellular localisation. In order to investigate these transient interactions, a bacterial two-hybrid system was employed. Interactions between CspE and HupA, a nucleoid protein identified in the proteomic analysis, were probed, as were interactions between CspE and CsdA, an RNA helicase thought to function co-operatively with CspE. The twohybrid system also allowed investigation of CspE dimerisation, which has been reported in vitro but not investigated in vivo until this study. CspE appears not to interact significantly with either HupA, CsdA, or itself at 37oC. Finally in a further attempt to identify interactions of CspE, a genomic library was created to test CspE interactions by two-hybrid assay with random peptides derived from the whole Salmonella genome. The library was successfully created and screened for evidence of interaction, and revealed an association between CspE and a transcriptional repressor, DeoT. DeoT is a repressor of several genes for catabolic processes, suggesting a role for CspE in the regulation of central metabolism. The findings of this work present a number of novel discoveries and several interesting opportunities for further studies.
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Yang, Hui. "Theoretical Studies of Molecular Recognition in Protein-Ligand and Protein-Protein Complexes." University of Toledo / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1282339026.
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Park, Changmoon Goddard William A. "Protein design and simulation Part I. Protein design. Part II. Protein simulation /." Diss., Pasadena, Calif. : California Institute of Technology, 1993. http://resolver.caltech.edu/CaltechTHESIS:11112009-114142428.
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Thesis (Ph. D.)--California Institute of Technology, 1993. UM #93-25,374.Advisor names found in the Acknowledgements pages of the thesis. Title from home page. Viewed 01/15/2010. Includes bibliographical references.
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Stains, Cliff. "Methods for the Detection of Protein-Nucleic Acid and Protein-Protein Interactions." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/194834.
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We describe the first general approach for the DNA templated reassembly of proteins, which we term SEquence-Enabled Reassembly or SEER. SEER makes use of dissected signaling domains which are each attached to separate, sequence specific DNA-binding proteins. Described herein is an embodiment of SEER in which DNA catalyzes the reassembly of the green fluorescent protein which leads to a direct fluorescence readout of the corresponding DNA sequence. This strategy has also been extended to the first direct method for the site specific detection of DNA methylation. This mCpG-SEER system is capable of discriminating between methylated versus nonmethylated DNA with a 40-fold increase in fluorescence signal.In a separate undertaking we tested the efficiency of disulfide bond formation within the context of the ribosome display in vitro selection methodology. We established conditions for the enrichment of a cyclic peptide, which is specific for Neutravidin, by 2 x 10^6-fold. Using the knowledge gained from the above experiments, we combined the rapid protein expression and folding benefits of cell-free translation systems with a sensitive split-luciferase reassembly assay to yield the most rapid method to date for the detection of protein-nucleic acid and protein-protein interactions. Furthermore, we have shown that these split-luciferase cell-free reassembly systems can be compartmentalized, allowing for future molecular evolution studies.Lastly, we have applied this rapid cell-free split-luciferase assay system to the direct detection of clinically relevant proteins. We have engineered a system for the rapid characterization of HIV-1 clades utilizing single-chain antibody specificities. We also demonstrate that this platform can be used to determine the relative amounts of HER2 expression in human breast cancer cells, using a homogeneous assay format in which cells and reagents are mixed and luminescence is monitored directly.We envision that the assay platforms described herein will find applications in the rapid detection of nucleic acid sequences, protein identities, and relative protein abundances in the laboratory and clinic.
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Boscolo, Cappon Jona <1988>. "DETECTIVE OVERLAPPING PROTEIN COMPLEXES IN PROTEIN-PROTEIN INTERACTION NETWORK USING DOMINANT SETS." Master's Degree Thesis, Università Ca' Foscari Venezia, 2013. http://hdl.handle.net/10579/2871.
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García-García, Javier 1982. "Protein-protein interaction network : management of databases and its applications on the computational study of protein-protein interactions." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/286512.
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The use of protein-protein interaction networks has become crucial due to the emergence of systems biology. The completeness and quality of networks, crucial to understand the biochemical mechanisms underlying a system such as a cell, are still challenging the scientific community. This thesis focuses on the data completeness challenge by the development of flexible tools for biological data management. It presents a database framework, BIANA, in which the integrated access to several information sources tackles this problem by unraveling hidden biological associations. BIANA is used to develop protein-protein interaction inference tools based on sequence similarity and protein-protein interactions. I have applied the approach on Salmonella-host infection, a case study where experimental data is scarce. Finally, I have focused on the integration problem of protein sequence annotation, also addressing the prediction of protein-protein interaction interfaces. I have developed a new evaluation measure to compare the predictive power of interface inference approaches.Les xarxes d'interacció proteïna-proteïna han esdevingut crucials des del naixement de la biologia de sistemes. La integritat i qualitat de les xarxes, que són essencials per entendre els mecanismes subjacents a un sistema com la cèl•lula, segueixen desafiant a la comunitat científica. Aquesta tesi se centra en el repte de la integritat de les dades mitjançant el desenvolupament d'eines flexibles per a la gestió de dades biològiques. Presento BIANA, un paquet informàtic que enfoca aquest problema facilitant l'accés integrat a diverses fonts d'informació. BIANA ha servit per desenvolupar eines de predicció d'interaccions proteïna-proteïna combinant les xarxes amb similitud entre seqüències. He aplicat aquest mètode sobre la infecció per Salmonella-hoste, un cas en el qual les dades experimentals són escasses. Finalment, m'he centrat en la integració associada a l'anotació de seqüències, abordant la predicció d'interfícies d'interacció proteïna-proteïna. Una nova mesura d'avaluació m'ha permès comparar el poder predictiu de diferents mètodes.
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Wu, Feihong. "Protein-protein interface database, analysis and prediction /." [Ames, Iowa : Iowa State University], 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3379186.
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Yu, Chao. "Matrix bound peptides modeling protein-protein interactions." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969927932.
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