Dissertations / Theses on the topic 'Protein binding – Mathematical models'
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Sidiqi, Mahjooba. "The structure and RNA-binding of poly (C) protein 1." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0077.
Full textGeli, Rolfhamre Patricia. "From penicillin binding proteins to community interventions : mathematical and statistical models related to antibiotic resistance /." Stockholm : Department of Mathematics, Stockholm University, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-8477.
Full textRoussel, Céline. "Etude du rôle des chélateurs calciques sur les oscillations du potentiel membranaire neuronal: approche expérimentale et théorique." Doctoral thesis, Universite Libre de Bruxelles, 2006. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210854.
Full textAu niveau théorique, nous avons élaboré un modèle mathématique de l’activité électrique du grain cérébelleux, prenant en compte la chélation du calcium intracellulaire. Il permet de clarifier le rôle de la chélation du calcium intracellulaire sur les oscillations du potentiel membranaire. La modélisation de l’activité électrique du grain cérébelleux repose sur le formalisme développé par Hodgkin et Huxley pour l’axone géant de calmar. Dans ce contexte, l’application de la conservation de la charge au circuit équivalent de la membrane cellulaire fournit un système d’équations différentielles ordinaires, non linéaires. Dès lors, notre modèle nous a permis d’étudier l’impact des variations de la concentration de chélateur calcique sur les oscillations du potentiel membranaire. Nous avons ainsi pu constater qu’une diminution de la concentration en chélateur calcique induisait une augmentation de l’excitabilité électrique du grain cérébelleux, sans altérer le régime d’oscillations. Par contre, en augmentant fortement la concentration en chélateur calcique, nous avons montré que le grain cérébelleux changeait de dynamique oscillatoire, montrant des transitions d’un mode de décharge périodique régulier vers des oscillations en salve du potentiel membranaire.
Au niveau expérimental, nous avons vérifié les résultats prévus par le modèle théorique. Nous avons ainsi montré que des grains de souris transgéniques déficientes en calrétinine présentaient une excitabilité électrique accrue par rapport aux grains contrôles.
Puis, en restaurant un niveau de chélation calcique normal dans ces grains, par perfusion intracellulaire de chélateur calcique, nous montrons qu’ils retrouvent un niveau d’excitabilité normal. Ensuite, nous avons introduit dans des grains cérébelleux de souris sauvages, une forte concentration en chélateur calcique exogène. Conformément aux résultats théoriques, nous avons pu observer des transitions vers des oscillations en salve du potentiel membranaire. Enfin, nous avons montré que l’absence de calrétinine affecte les paramètres morphologiques du grain cérébelleux des souris transgéniques déficientes en calrétinine.
En conclusion, ces résultats suggèrent que le mode de décharge des cellules excitables peut être modulé d’une façon importante par les protéines liant le calcium. De ce fait, des changements dans le niveau d’expression et/ou dans la localisation subcellulaire des protéines liant le calcium pourraient aussi jouer un rôle critique dans la régulation de processus physiologiques contrôlés par l’excitabilité membranaire. De plus, les mécanismes que nous avons mis en évidence pourraient être à l’origine d’un nouveau principe de régulation de la signalisation dans les circuits neuronaux et pourraient jouer un rôle fonctionnel dans le contrôle du codage de l’information et de son stockage dans le système nerveux central.
Doctorat en sciences, Spécialisation physique
info:eu-repo/semantics/nonPublished
Hinkle, Adam R. "Tight-binding calculation of electronic properties of oligophenyl and oligoacene nanoribbons." Virtual Press, 2008. http://liblink.bsu.edu/uhtbin/catkey/1398716.
Full textDepartment of Physics and Astronomy
Chiang, T. "Mathematical and statistical models for the analysis of protein." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597600.
Full textGregor, Craig Robert. "Epitopes, aggregation and membrane binding : investigating the protein structure-function relationship." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/5833.
Full textAllison, Jerry Dewell. "An implementation of the competitive Gaussian model for metal-humic binding in a general speciation model." Diss., Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/25965.
Full textNordling, Erik. "Biocomputational studies on protein structures /." Stockholm, 2002.
Find full textSmoler, Eliezer. "Mathematical models to predict milk protein concentration from dietary components fed to dairy cows." Thesis, University of Reading, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308060.
Full textChu, Vano. "Molecular recognition in the streptavidin-biotin system /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/8106.
Full textAdhikari, Sombudha. "IDENTIFICATION OF PROTEIN PARTNERS FOR NIBP, A NOVEL NIK-AND IKKB-BINDING PROTEIN THROUGH EXPERIMENTAL, COMPUTATIONAL AND BIOINFORMATICS TECHNIQUES." Master's thesis, Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/216569.
Full textM.S.
NIBP is a prototype member of a novel protein family. It forms a novel subcomplex of NIK-NIBP-IKKB and enhances cytokine-induced IKKB-mediated NFKB activation. It is also named TRAPPC9 as a key member of trafficking particle protein (TRAPP) complex II, which is essential in trans-Golgi networking (TGN). The signaling pathways and molecular mechanisms for NIBP actions remain largely unknown. The aim of this research is to identify potential proteins interacting with NIBP, resulting in the regulation of NFKB signaling pathways and other unknown signaling pathways. At the laboratory of Dr. Wenhui Hu in the Department of Neuroscience, Temple University, sixteen partner proteins were experimentally identified that potentially bind to NIBP. NIBP is a novel protein with no entry in the Protein Data Bank. From a computational and bioinformatics standpoint, we use prediction of secondary structure and protein disorder as well as homology-based structural modeling approaches to create a hypothesis on protein-protein interaction between NIBP and the partner proteins. Structurally, NIBP contains three distinct regions. The first region, consisting of 200 amino acids, forms a hybrid helix and beta sheet-based domain possibly similar to Sybindin domain. The second region comprised of approximately 310 residues, forms a tetratrico peptide repeat (TPR) zone. The third region is a 675 residue long all beta sheet and loops zone with as many as 35 strands and only 2 helices, shared by Gryzun-domain containing proteins. It is likely to form two or three beta sheet sandwiches. The TPR regions of many proteins tend to bind to the peptides from disordered regions of other proteins. Many of the 16 potential binding proteins have high levels of disorder. These data suggest that the TPR region in NIBP most likely binds with many of these 16 proteins through peptides and other domains. It is also possible that the Sybindin-like domain and the Gryzun-like domain containing beta sheet sandwiches bind to some of these proteins.
Temple University--Theses
Balderson, Stephanie D. "Investigations of Insulin-Like Growth Factor I Cell Surface Binding: Regulation by Insulin-Like Growth Factor Binding Protein-3 and Heparan Sulfate Proteoglycan." Thesis, Virginia Tech, 1997. http://hdl.handle.net/10919/30494.
Full textMaster of Science
Henne, Randal Marlow. "Computational studies of G-protein coupled receptors /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8048.
Full textBrown, Jennifer Louise. "Investigation of the molecular interactions between an anti-peptide antibody and its ligand." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318221.
Full textRobertson, Timothy Allen. "Development and validation of statistical potential functions for the prediction of protein/nucleic-acid interactions from structure /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/9268.
Full textGe, Wanwan [Verfasser]. "Discovery and prediction of protein binding sites in DNA and RNA sequences using Bayesian Markov models / Wanwan Ge." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/1236753968/34.
Full textLee, Pui-chi, and 李佩芝. "Phenotypic characterization of adipocyte fatty acid binding protein knockout mice under high fat high cholesterol diet-induced obesity." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197517.
Full textpublished_or_final_version
Medicine
Master
Master of Philosophy
Tsilo, Lipontseng Cecilia. "Protein secondary structure prediction using neural networks and support vector machines." Thesis, Rhodes University, 2009. http://hdl.handle.net/10962/d1002809.
Full textGaudreault, Mathieu. "Collapse transition of SARWs with hydrophobic interaction on a two dimensional lattice." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112623.
Full textBetz, Michael [Verfasser], and Gerhard [Akademischer Betreuer] Klebe. "Development of models to describe the dynamics and interaction with water molecules in protein-ligand binding / Michael Betz. Betreuer: Gerhard Klebe." Marburg : Philipps-Universität Marburg, 2015. http://d-nb.info/1081215569/34.
Full textYe, Dewei, and 叶得伟. "Toll-like receptor-4 mediates obesity-induced nonalcoholic steatohepatitis through activation of X-box binding protein-1 in mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47752919.
Full textpublished_or_final_version
Medicine
Doctoral
Doctor of Philosophy
Nelson, Michael R. Jr. "Ab initio molecular orbital studies: Rydberg states of H₄ barriers to internal rotation studies binding of CO₂ to carbonyl groups isoprene and ozone complexes." Diss., Georgia Institute of Technology, 1998. http://hdl.handle.net/1853/30278.
Full textSubramanian, Kartik. "Spatiotemporal Model of the Asymmetric Division Cycle of Caulobacter crescentus." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/65156.
Full textPh. D.
Kambafwile, Henry Kunda. "Synthesis of activity-based protein profiling probes for malaria and hypertension disease models & potential novel ACE inhibitors with an attenuated zinc binding group." Doctoral thesis, University of Cape Town, 2012. http://hdl.handle.net/11427/11736.
Full textAngiotensin-converting enzyme (ACE) and P. falciparum A M1 (PfA-M1) are both zinc metalloproteases implicated in hypertension and malaria, respectively. Hypertension affects approximately 26 % of the world’s population while each year over 300 million cases of malaria occur worldwide resulting in between 1.5 and 2.7 million deaths annually. Hypertension treatment with current ACE inhibitors is marred by unpleasant side effects, such as cough and angioedema. In malaria, the parasites continuously develop resistance to anti-malarial drugs where the disease is endemic. There is therefore a need for continuous research into the application of new techniques as well as the design of new small molecule chemical entities as probes or chemotherapeutic agents.
Xian, Lede. "Electronic structure and interlayer coupling in twisted multilayer graphene." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/51811.
Full textFisch, Thomas Martin. "Effects of insulin-like growth factor-binding protein-2 (IGFBP-2) overexpression on adrenal and renal growth processes and functions: findings in transgenic mouse models." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-34045.
Full textScott, Carol Elizabeth DeWeese. "Molecular modeling and experimental characterization of HLA-DQ proteins and protein/peptide complexes : correlation with insulin-dependent diabetes mellitus (IDDM) /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/8089.
Full textKaminishi, Tatsuya, Andreas Schedlbauer, Attilio Fabbretti, Letizia Brandi, Lizarralde Borja Ochoa, Cheng-Guang He, Pohl Milon, Sean R. Connell, Claudio O. Gualerzi, and Paola Fucini. "Crystallographic characterization of the ribosomal binding site and molecular mechanism of action of Hygromycin A." Oxford University Press, 2015. http://hdl.handle.net/10757/608247.
Full textBizkaia:Talent and the European Union's Seventh Framework Program (Marie Curie Actions; COFUND; to S.C., A.S., T.K.); Marie Curie Actions Career Integration Grant (PCIG14-GA-2013-632072 to P.F.); Ministerio de Economía Y Competitividad (CTQ2014-55907-R to P.F., S.C.); FIRB Futuro in Ricerca from the Italian Ministero dell'Istruzione, dell'Universitá e della Ricerca (RBFR130VS5_001 to A.F.); Peruvian Programa Nacional de Innovación para la Competitividad y Productividad (382-PNICP-PIBA-2014 (to P.M. and A.F.)). Funding for open access charge: Institutional funding.
Revisión por pares
Hubig, Christina Stefanie [Verfasser]. "Investigations on the role of the IGF2 mRNA-binding protein p62 and the long non-coding RNA H19 in cell culture and in vivo models of hepatocellular carcinoma / Christina Stefanie Hubig." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2018. http://d-nb.info/1174876999/34.
Full textChou, Chiu-wen, and 周秋雯. "A study of the expression of NF-kB in central nervous system of rats with neuropathic pain." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44902542.
Full textGebski, Bijanka L. "Investigating TNF inhibition of IGF-1 signalling via JNK in cell culture models of skeletal muscle atrophy." University of Western Australia. School of Anatomy and Human Biology, 2009. http://theses.library.uwa.edu.au/adt-WU2010.0097.
Full textRivas, Cruz Manuel A. "Medical relevance and functional consequences of protein truncating variants." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:a042ca18-7b35-4a62-aef0-e3ba2e8795f7.
Full textLagerquist, Hägglund Christine. "Affinity-, Partition- and Permeability Properties of the Human Red Blood Cell Membrane and Biomembrane Models, with Emphasis on the GLUT1 Glucose Transporter." Doctoral thesis, Uppsala University, Department of Biochemistry, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3525.
Full textThe human glucose transporter GLUT1 is abundant in red blood cells, the blood-brain barrier and epithelial cells, where it mediates the transport of the energy metabolite, glucose. In the present work some properties of GLUT1, including affinity binding of both substrates and inhibitors, transport rates as well as permeabilities of aromatic amino acids and drug-membrane interactions were analyzed by chromatographic methods.
Reconstitution by size-exclusion chromatography on Superdex 75 from a detergent with a low CMC that provides monomeric GLUT1 was examined regarding D-glucose- and CB binding as well as D-glucose transport. Upon steric immobilization in Superdex 200 gel beads, residual detergent could be washed away and dissociation constants in the same range as reported for binding to GLUT1 reconstituted from other detergents were obtained. The transport rate into the GLUT1 proteoliposomes was low, probably due to residual detergent. Binding to GLUT1 at different pH was analyzed and the affinity of glucose and GLUT1 inhibitors was found to decrease with increasing pH (5–8.7). The average number of cytochalasin B-binding sites per GLUT1 monomers was, in most cases, approximately 0.4. GLUT1 may work as a functional monomer, dimer or oligomer. To determine whether GLUT1 was responsible for the transport of the aromatic amino acids tyrosine and tryptophan, uptake values and permeabilities of these amino acids into liposomes and GLUT1 proteoliposomes were compared to the permeabilities of D- and L- glucose in the same systems. Dihydrocytochalasin B was identified to be a new inhibitor of tyrosine and tryptophan transport into red blood cells. Ethanol turned out to inhibit the specific binding between CB and GLUT1 and also to decrease the partitioning of CB and drugs into lipid bilayers. A capacity factor for drug partitioning into membranes that allows comparison between columns with different amount of immobilized lipids was validated, and turned out to be independent of flow rate, amount of lipids and drug concentration in the ranges tested.
Leon, Ronald P. "Structural and functional analysis of MCM helicases in eukaryotic DNA replication /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
Find full textTypescript. Includes bibliographical references (leaves 90-98). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
Yasmin, Lubna. "Exoenzyme S of Pseudomonas aeruginosa : cellular targets and interaction with 14-3-3." Doctoral thesis, Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1411.
Full textLe, Treut Guillaume. "Models of chromosome architecture and connection with the regulation of genetic expression." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS411/document.
Full textIncreasing evidences suggest that chromosome folding and genetic expression are intimately connected. For example, the co-expression of a large number of genes can benefit from their spatial co-localization in the cellular space. Furthermore, functional structures can result from the particular folding of the chromosome. These can be rather compact bundle-like aggregates that prevent the access to DNA, or in contrast, open coil configurations with several (presumably) globular clusters like transcription factories. Such phenomena have in common to result from the binding of divalent proteins that can bridge regions sometimes far away on the DNA sequence. The physical system consisting of the chromosome interacting with divalent proteins can be very complex. As such, most of the mechanisms responsible for chromosome folding and for the formation of functional structures have remained elusive.Using methods from statistical physics, we investigated models of chromosome architecture. A common denominator of our approach has been to represent the chromosome as a polymer with bending rigidity and consider its interaction with a solution of DNA-binding proteins. Structures entailed by the binding of such proteins were then characterized at the thermodynamical equilibrium. Furthermore, we complemented theoretical results with Brownian dynamics simulations, allowing to reproduce more of the biological complexity.The main contributions of this thesis have been: (i) to provide a model for the existence of transcrip- tion factories characterized in vivo with fluorescence microscopy; (ii) to propose a physical basis for a conjectured regulatory mechanism of the transcription involving the formation of DNA hairpin loops by the H-NS protein as characterized with atomic-force microscopy experiments; (iii) to propose a physical model of the chromosome that reproduces contacts measured in chromosome conformation capture (CCC) experiments. Consequences on the regulation of transcription are discussed in each of these studies
Rodrigues, Christelle. "Optimisation des posologies des antiépileptiques chez l’enfant à partir de données pharmacocinétiques pédiatriques et adultes Population pharmacokinetics of oxcarbazepine and its monohydroxy derivative in epileptic children A population pharmacokinetic model taking into account protein binding for the sustained-release granule formulation of valproic acid in children with epilepsy Conditional non-parametric bootstrap for non-linear mixed effect models Pharmacokinetics evaluation of vigabatrin dose for the treatment of refractory focal seizures in children using adult and pediatric data Pharmacokinetic extrapolation from adult to children in case of nonlinear elimination: a case study." Thesis, Sorbonne Paris Cité, 2018. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2398&f=17336.
Full textChildren greatly differ from adults not only in terms of size but also in physiological terms. Indeed, developmental changes occur during growth due to maturation. These processes occur in a nonlinear fashion and can cause pharmacokinetic and pharmacodynamic differences. Thus, oppositely to common practice, it is not appropriate to scale pediatric doses directly and linearly from adults. The study of pharmacokinetics in children is then essential to determine those pediatric dosages. The more commonly used methodology is population analysis through non-linear mixed effects models. This method allows the analysis of sparse and unbalanced data. In return, the lack of individual data has to be balanced with the inclusion of more individuals. This can be a problem when the indication of treatment is a rare disease, as are epileptic syndromes of childhood. In this case, extrapolation of adult pharmacokinetic models to the pediatric population may be interesting. The objective of this thesis was to evaluate the dosage recommendations of antiepileptic drugs when pediatric pharmacokinetic data are sufficient to be modeled, and when they are not, extrapolating adequately adult information. Firstly, a parent-metabolite model of oxcarbazepine and its monohydroxy derivative (MHD) was developed in epileptic children aged 2 to 12 years. This model showed that younger children require higher doses, as well as patients co-treated with enzyme inducers. A model was also developed for epileptic children aged 1 to 18 years treated with a valproic acid sustained release microsphere formulation. This model took into account the flip-flop associated with the formulation and the non-linear relationship between clearance and dose caused by a saturable protein binding. Again, the need for higher doses for younger children was highlighted. Then, an adult model of vigabatrin was extrapolated to children to determine which doses allow to achieve exposures similar to adults in resistant focal onset seizures. From the results obtained, which are in agreement with the conclusions of clinical trials, we have been able to propose an ideal maintenance dose for this indication. Finally, we studied the relevance of extrapolation by theoretical allometry in a context of non-linearity with the example of stiripentol. We concluded that this method seems to provide good predictions from the age of 8, unlike the linear elimination molecules where it seems correct from 5 years. In conclusion, we were able to test and compare different approaches to help determine dosing recommendations in children. The study of pediatric pharmacokinetics in specific trials remains essential for the proper use of drugs
Barwich, Ann-Sophie. "Making sense of smell : classifications and model thinking in olfaction theory." Thesis, University of Exeter, 2013. http://hdl.handle.net/10871/13869.
Full text"Clues of identification of protein-protein interaction sites." 2005. http://library.cuhk.edu.hk/record=b5892544.
Full textThesis submitted in: November 2004.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2005.
Includes bibliographical references (leaves 67-71).
Abstracts in English and Chinese.
Abstract
Chapter CHAPTER 1. --- INTRODUCTION --- p.1
Chapter 1.1 --- Background of protein structures --- p.1
Chapter 1.2 --- Background of protein-protein interaction (PPI) --- p.4
Chapter 1.2.1 --- Quaternary structure and protein complex --- p.4
Chapter 1.2.2 --- Previous related work --- p.4
Chapter 1.2.3 --- The kinetic and thermodynamic formalism --- p.6
Chapter CHAPTER 2. --- MATERIALS AND METHODS --- p.10
Chapter 2.1 --- Amino acid composition representative power modeling --- p.10
Chapter 2.1.1 --- Propensity level modeling --- p.10
Chapter 2.1.2 --- Polar atoms visualization --- p.17
Chapter 2.2 --- Rigid structure representative power modeling --- p.17
Chapter 2.3 --- Electrostatic potential modeling --- p.17
Chapter 2.3.1 --- Charge residence --- p.17
Chapter 2.3.2 --- Minimum Ribbon (MR) --- p.19
Chapter 2.4 --- Examination of interface --- p.23
Chapter 2.5 --- Identification procedures of a binding site --- p.24
Chapter 2.6 --- System requirements --- p.24
Chapter CHAPTER 3. --- RESULTS AND DISCUSSIONS --- p.24
Chapter 3.1 --- Polar atoms --- p.25
Chapter 3.2 --- Minimum Ribbon (MR) --- p.27
Chapter 3.3 --- "Charge complementarity, propensity level and rigid structure orientation" --- p.31
Chapter 3.4 --- Identification of interacting site --- p.36
Chapter CHAPTER 4. --- CONCLUSIONS --- p.64
System requirements --- p.65
Basic operation --- p.65
Limitation --- p.66
Hicks, Joshua M. "Analysis of secondary structures in nucleic acid binding proteins and nuclear magnetic resonance investigation of helix propagation and residual motions in proteins." Thesis, 2005. http://hdl.handle.net/1957/29424.
Full text"Pattern discovery for deciphering gene regulation based on evolutionary computation." Thesis, 2010. http://library.cuhk.edu.hk/record=b6075246.
Full textTF-TFBS associated sequence pattern (rule) discovery is further investigated for better deciphering protein-DNA interactions in regulation. We for the first time generalize previous exact TF-TFBS rules to approximate ones using a progressive approach. A customized algorithm is developed, outperforming MEME by over 73%. The approximate TF-TFBS rules, compared with the exact ones, have significantly more verified rules and better verification ratios. Detailed analysis on PDB cases and conservation verification on NCBI protein records illustrate that the approximate rules reveal the flexible and specific protein-DNA interactions with much greater generalized capability.
The comprehensive pattern discovery algorithms developed will be further verified, improved and extended to further deciphering transcriptionial regulation, such as inferring whole gene regulatory networks by applying TFBS and TF-TFBS patterns discovered and incorporating expression data.
Transcription Factor (TF) and Transcription Factor Binding Site (TFBS) bindings are fundamental protein-DNA interactions in transcriptional regulation. TFs and TFBSs are conserved to form patterns (motifs) due to their important roles for controlling gene expressions and finally affecting functions and appearances. Pattern discovery is thus important for deciphering gene regulation, which has tremendous impacts on the understanding of life, bio-engineering and therapeutic applications. This thesis contributes to pattern discovery involving TFBS motifs and TF-TFBS associated sequence patterns based on Evolutionary Computation (EC), especially Genetic Algorithms (GAs), which are promising for bioinformatics problems with huge and noisy search space.
Chan, Tak Ming.
Advisers: Kwong-Sak Leung; Kin-Hong Lee.
Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 147-153).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
Al-Malah, Kamal Issa Masoud. "Macroscopic model for apparent protein adsorption equillibrium at hydrophobic solid-water interfaces." Thesis, 1993. http://hdl.handle.net/1957/35391.
Full textGroh, C. M., M. E. Hubbard, P. F. Jones, Paul M. Loadman, Nagarajan Periasamy, B. D. Sleeman, S. W. Smye, Christopher J. Twelves, and Roger M. Phillips. "Mathematical and computational models of drug transport in tumours." 2014. http://hdl.handle.net/10454/10002.
Full textThe ability to predict how far a drug will penetrate into the tumour microenvironment within its pharmacokinetic (PK) lifespan would provide valuable information about therapeutic response. As the PK profile is directly related to the route and schedule of drug administration, an in silico tool that can predict the drug administration schedule that results in optimal drug delivery to tumours would streamline clinical trial design. This paper investigates the application of mathematical and computational modelling techniques to help improve our understanding of the fundamental mechanisms underlying drug delivery, and compares the performance of a simple model with more complex approaches. Three models of drug transport are developed, all based on the same drug binding model and parametrized by bespoke in vitro experiments. Their predictions, compared for a ‘tumour cord’ geometry, are qualitatively and quantitatively similar. We assess the effect of varying the PK profile of the supplied drug, and the binding affinity of the drug to tumour cells, on the concentration of drug reaching cells and the accumulated exposure of cells to drug at arbitrary distances from a supplying blood vessel. This is a contribution towards developing a useful drug transport modelling tool for informing strategies for the treatment of tumour cells which are ‘pharmacokinetically resistant’ to chemotherapeutic strategies.
Poiares, João Pedro da Silva Gonçalves. "Development of a QSAR models for the prediction of plasma protein binding." Master's thesis, 2014. http://hdl.handle.net/10437/5858.
Full textOne of the most important factors, affecting the pharmacokinetic profile of a drug is binding to plasma protein. As such, this study aimed at the development of a quantitative structure–activity relationship model, to predict the fraction unbound in plasma (fub) for four species, using artificial neural network ensemble (ANNE). To this end a database of 363 drugs was used, and molecular descriptors were determined. The dataset was divided in two groups, a train and an external validation, to avoid overfitting. The ANNE optimization reduced the descriptors required to determine the fub to 37, and 150 ANN were randomly selected, trained and the optimal configuration was collected. The different ANNE were built by averaging the output values of the selected ANN and the best ANNE was selected. The model created was able to predict, with a small amount of error, the fub values (root mean square error of 0.16798 and 0.193705 for train and test dataset respectively), however, it tends to underestimate this value (mean error of -0.00291 and -0.015780 for train and test dataset respectively). The ANNE interpretation showed that the main characteristics of that affect fub were the molecule charge, size, structure and lipophilic and hydrophilic affinity.
Um dos factores mais influentes na farmacocinética deum fármaco é a ligação às proteínas plasmáticas. Sendo assim, com este estudo pretendeu -se desenvolver um modelo QSAR, para prever facção do fármaco livre no plasma (fub)para quatro espécies, usando um “ensamble ”de redes neuronais (ANNE). Para tal, utilizou –se uma base – de -dados de 363 fármacos, e determinou-se os seus descritores moleculares. Esta base de dados foi dividida em dois grupos, um para treino e outro para validação externa, para evitar “overfitting”. O ANNE foi optimizado, reduzindo o número de descritores para 37, e 150 redes foram aleatoriamente selecionadas, treinadas e a sua configuração optimizada registada. Os diversos ANNE foram obtido através da média aritmética dos valores das redes seleccionadas, e o melhor ANNE foi escolhido. Este modelo foi capaz de prever com um erro reduzido, o valor da fub (erro quadrático médio de 0.16798 e0.193705 para o grupo de treino e teste respectivamente), no entanto tendencialmente subestima o seu valor (erro médio de -0.00291 e -0.015780 para o grupo de treino e teste respectivamente) . A interpretação do modelo permitiu observar que o tamanho da molécula, a sua estrutura, carga, lipofilia e hidrofilia são as características que mais afectam o valor da fub.
Hsieh, Chun-Chih, and 謝濬智. "Estimating Protein and Amino Acid Requirements of Taiwan Native Chickens by Mathematical Models." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/71195527940275502211.
Full text東海大學
畜產與生物科技學系
93
The objective of this study was to estimate the protein and amino acid (AA) requirement of Taiwan native chickens during 0 to 16 wks by mathematical models. 125 one-day-old four-way crossbred Taiwan native male and female chickens (Taishi Meat No. 13) were divided into five pens with 25 chickens each, respectively. One chicken from each pen closest to the mean body weight were selected weekly, killed and their body and feather protein contents were measured. All the chickens were fed a commercial diet in an open-type house. Gompertz growth function was used to estimate the growth curve of the chickens; it was further modified and differentiated to calculate the daily body protein deposition rate (dBP/dt) and the daily feather protein deposition rate (dFP/dt) of chickens; linear regression equation was used to calculate the daily body protein requirement for growth (BPG) and the daily feather protein requirement for growth (FPG) of chickens. The daily body protein requirement for maintenance (MPB) and the daily feather protein requirement for maintenance (MPF) was added beyond them, namely AAR=[p dBP/dt+q dFP/dt]/0.8+[p MPB+q MPF] (Gompertz growth model) and AAR=[p BPG+q FPG]/0.8+[p MPB+q MPF] (linear regression) to give the daily digestible protein and AA requirement, where AAR is the daily digestible AA requirement (g/d), p is the individual AA contents of body protein (g/kg), q is the individual AA contents of feather protein (g/kg) and 0.8 is the utilized efficiency of AA. The results indicated that the daily digestible protein and AA requirements increased curvilinearly with increasing age. They reached a plateau at day 56~63 and 63~70 in male and female, respectively, when the weight gain of them reached the plateau. After that, they decreased curvilinearly when weight gain passed the plateau. The daily digestible protein and AAR of male was significant higher than that of female. The curvilinear relationship between daily digestible protein requirement and body weight were: y = 1.17 + 9.83x — 4.46x2 (male; R2 = 0.98, P < 0.01), y = 1.09 + 8.49x — 5.02x2 (female; R2 = 0.96, P < 0.01) estimated by Gompertz growth model; y = 0.59 + 10.86x — 4.85x2 (male; R2 = 0.98, P < 0.01), y = 0.39 + 9.29x — 4.99x2 (female; R2 = 0.98, P < 0.01) estimated by linear regression. Where y is daily protein requirement (g/d), x = body weight (kg). AA requirement followed similar curvilinear curve as of protein requirement. Our estimated requirements could be used as a reference to determine the protein and AA requirements of Taiwan native chickens in different age, sex and growth rate.
He, Rong-Heng, and 何榕恒. "FK506-Binding Protein 51 Regulates GABAergic Neurotransmission-related Protein Expression in Peripheral Inflammation- versus Glucocorticoid- induced Anxiety Mouse Models." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/16676195364561600806.
Full textBarrientos, KS, MF Kendellen, BD Freibaum, BN Armbruster, KT Etheridge, and CM Counter. "Distinct functions of POT1 at telomeres." Thesis, 2008. http://hdl.handle.net/10161/1343.
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Gumede, Njabulo Joyfull. "Computational and micro-analytical techniques to study the in vitro and in silico models of novel therapeutic drugs." Thesis, 2016. http://hdl.handle.net/10321/1751.
Full textIn drug discovery and development projects, metabolism of new chemical entities (NCEs) is a major contributing factor for the withdrawal of drug candidates, a major concern for other chemical industries where chemical-biological interactions are involved. NCEs interact with a target macro-molecule to stimulate a pharmacological or toxic response, known as pharmacodynamics (PD) effect or through the Adsorption, Distribution, Metabolism, and Excretion (ADME) process, triggered when a bio-macromolecule interacts with a therapeutic drug. Therefore, the drug discovery process is important because 75% of diseases known to human kind are not all cured by therapeutics currently available in the market. This is attributed to the lack of knowledge of the function of targets and their therapeutic use in order to design therapeutics that would trigger their pharmacological responses. Accordingly, the focus of this work is to develop cost saving strategies for medicinal chemists involved with drug discovery projects. Therefore, studying the synergy between in silico and in vitro approaches maybe useful in the discovery of novel therapeutic compounds and their biological activities. In this work, in silico methods such as structure-based and ligand-based approaches were used in the design of the pharmacophore model, database screening and flexible docking methods. Specifically, this work is presented by the following case studies: The first involved molecular docking studies to predict the binding modes of catechin enantiomer to human serum albumin (HSA) interaction; the second involved the use of docking methods to predict the binding affinities and enantioselectivity of the interaction of warfarin enantiomers to HSA. the third case study involved a combined computational strategy in order to generate information on a diverse set of steroidal and non-steroidal CYP17A1 inhibitors obtained from literature with known experimental IC50 values. Finally, the fourth case study involved the prediction of the site of metabolisms (SOMs) of probe substrates to Cytochrome P450 metabolic enzymes CYP 3A4, 2D6, and 2C9 making use of P450 module from Schrödinger suite for ADME/Tox prediction. The results of case study I were promising as they were able to provide clues to the factors that drive the synergy between experimental kinetic parameters and computational thermodynamics parameters to explain the interaction between drug enantiomers and thetarget protein. These parameters were correlated/converted and used to estimate the pseudo enantioselectivity of catechin enantiomer to HSA. This approach of combining docking methodology with docking post-processing methods such as MM-GBSA proved to be vital in estimating the correct pseudo binding affinities of a protein-ligand complexes. The enantioselectivity for enantiomers of catechin to HSA were 1,60 and 1,25 for site I and site II respectively. The results of case study II validates and verifies the preparation of ligands and accounting for tautomers at physiological pH, as well as conformational changes prior to and during docking with a flexible protein. The log KS = 5.43 and log KR = 5.34 for warfarin enantiomer-HSA interaction and the enantioselectivity (ES = KS/KR) of 1.23 were close to the experimental results and hence referred to as experimental-like affinity constants which validated and verified their applicability to predict protein-ligand binding affinities. In case study III, a 3D-QSAR pharmacophore model was developed by using 98 known CYP17A1 inhibitors from the literature with known experimental IC50 values. The starting compounds were diverse which included steroidal and non-steroidal inhibitors. The resulting pharmacophore models were trained with 69 molecules and 19 test set ligands. The best pharmacophore models were selected based on the regression coefficient for a best fit model with R2 (ranging from 0.85-0.99) & Q2 (ranging from 0.80-0.99) for both the training and test sets respectively, using Partial Least Squares (PLS) regression. On the other hand, the best pharmacophore model selected was further used for a database screening of novel inhibitors and the prediction of their CYP17A1 inhibition. The hits obtained from the database searches were further subjected to a virtual screening workflow docked to CYP17A1 enzyme in order to predict the binding mode and their binding affinities. The resulting poses from the virtual screening workflow were subjected to Induced Fit Docking workflow to account for protein flexibility during docking. The resulting docking poses were examined and ranked ordered according to the docking scores (a measure of affinity). Finally, the resulting hits designed from an updated model from case study III were further synthesized in an external organic chemistry laboratory and the synthetic protocols as well as spectroscopic data for structure elucidation forms part of the provisional patent specification. A provisional patent specification has been filed (RSA Pat. Appln. 2015/ 07849). The case studies performed in this thesis have enabled the discovery of non-steroidal CYP17A1 inhibitors.
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Dang, Truong Khanh Linh. "Probabilistic Models to Detect Important Sites in Proteins." Doctoral thesis, 2020. http://hdl.handle.net/21.11130/00-1735-0000-0005-1583-F.
Full textLehrer, Helaina. "Investigating the role of the RNA binding protein TDP-43 in Amyotrophic Lateral Sclerosis using animal and cell-based models of disease." Thesis, 2015. https://doi.org/10.7916/D8G44PJQ.
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