Dissertations / Theses on the topic 'In silico screening'
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Dunkel, Mathias [Verfasser]. "3D Konformationsdatenbanken für das in silico Screening / Mathias Dunkel." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2008. http://d-nb.info/1023262142/34.
Full textBarakat, Nora Hisham. "Combining in vivo and in silico screening for protein stability." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3258327.
Full textTitle from first page of PDF file (viewed May 29, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 137-152).
Füllbeck, Melanie. "In silico und in vitro Screening von Proteinliganden zur Apoptoseinduktion." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15702.
Full textNowadays, cancer research is focused on the overcoming of survival strategies of malign tumors. In the present work, computer-based methods lead to the identification of novel apoptosis inducing molecules, whose potency should be validated in in vitro experiments. Novel compounds, which induce apoptosis in cancer cells, could be identified on the basis of three projects. Inhibitors for the COP9 signalosome (CSN) associated kinases CK2 and PKD could be discovered using curcumin and emodin as lead compounds. Investigations concerning the mechanism-of-action of betulinic acid (BA) should give information about the function of the Bcl-2 protein family in the BA induced cell death. The experiments, which are focused on the mitochondrial signalling pathway, revealed that BA induces apoptosis in an almost independent manner with regards to the pro- and anti-apoptotic Bcl-2 proteins, but dependent on the presence of activated caspases. Via an in silico screening and the utilisation of a new property filter, novel BA analogues could be identified. For the first time, the data of the National Cancer Institute (NCI) is employed to evaluate results from the in silico screening. In the third project two novel Bcl-2 inhibitors have been identified via in silico screenings, docking experiments and in vitro screenings, which are performed at the moment. The insertion of a photo-switchable compound to the amino acid side chain of an alpha-helical peptide from the pro-apoptotic protein Bid triggered the effect of a modulator, which results in a controllable activation and initiation of apoptosis in tumor cells. In silico screenings as a reliable method corroborated that a systematical evaluation of the virtual hits could decrease the time and costs of experimental testings. The identified hits could serve as novel lead compounds for further in silico screenings or enter the next steps in the development of novel drugs using optimisation methods.
Harding, Simon D. "Database analysis of protein-peptide interactions and in silico screening for peptidomimetics." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/10935.
Full textSalentin, Sebastian. "In Silico Identification of Novel Cancer Drugs with 3D Interaction Profiling." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2018. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-226435.
Full textYoungs, Louise Claire. "Evaluation of in silico and in vitro screening methods for characterising endocrine disrupting chemical hazards." Thesis, Cranfield University, 2014. http://dspace.lib.cranfield.ac.uk/handle/1826/9717.
Full textElkaïm, Judith. "Drug design in silico : criblage virtuel de protéines à visée thérapeutique." Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14444/document.
Full textThe process of drug discovery is long and tedious. Besides, it is relatively inefficient in terms of hit rate. The identification of candidates through experimental testing is expensive and requires extensive data on the mechanisms of the target protein in order to develop efficient assays. Virtual screening can considerably accelerate the process by quickly evaluating large databases of compounds and determining the most likely to bind to a target. Some success stories have emerged in the field over the last few years.The objectives of this work were first, to compare common tools and strategies for structure-based virtual screening, and second, to apply those tools to actual target proteins implied notably in carcinogenesis.In order to evaluate the docking and scoring programs available, the protein kinase GSK3 and a test set of known ligands were used as a model to perform methodological studies. In particular the influence of the flexibility of the protein was explored via relaxed structures of the receptor or the insertion of torsions on the side chains of residues located in the binding site. Studies concerning the automatic generation of 3D structures for the ligands and the use of consensus scoring also provided insights on the usability of these tools while performing a virtual screening.Virtual screening of the human protein Pontin, an ATPase implied in tumor cell growth for which no inhibitors were known, allowed the prioritization of compounds from commercial databases. These compounds were tested in an enzymatic assay via a collaboration, and led to the identification of four molecules capable of inhibiting the ATPase activity of Pontin. Additional screens of in-house oriented databases also provided at least one innovative inhibitor for this protein. On the contrary, a study of the human PLA2-X, a phospholipase that requires a Ca2+ atom to bind to its active site in order to catalyze the hydrolysis of its substrate, revealed the limits of our docking tools that could not handle the metal ion and the need for new tools
Šramel, Peter. "A synthesis and biological screening of predicted inhibitors of Tyrosine Kinases, e.g. KDR, designed in silico." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF064.
Full textProtein kinases represent a group of enzymes responsible for phosphorylation - transfer of aphosphate group from adenosine triphosphate (ATP) to tyrosine or serine/threonine residues. Protein phosphorylation is one of the most important tools regulating a cell activity. A cell "signalization" through an endothelial receptor tyrosine kinase VEGFR2 TK (KDR) is the important pathway influencing growth of a tumor. Small-molecule inhibitors of VEGFR2 TK (VEGFR2 TKls) have become an important tool for the treatment of various types of cancer. This dissertation thesis resulted in a discovery of 16 biologically active N,5-diaryloxazol-2-amines (IC50, VEGFR2 TK). Very good results were achieved especially with compounds 189, 191, 211, 214, 220, 221, 223 and 4 exhibiting the activity under 500 nM
Tichauer, Ruth Elena. "In silico screening of NRas protein oncogenic mutations : new structural and physico-chemical insights into the catalytic activity." Electronic Thesis or Diss., Toulouse 3, 2019. http://www.theses.fr/2019TOU30028.
Full textRas subfamily of small GTPase proteins holds a key position in cell proliferation pathways. Indeed, the transmission of cell growth signals is controlled by proteins belonging to it. In their GTP-bound conformation, these proteins interact and activate downstream effectors of cell replication and differentiation. The hydrolysis reaction that takes place in their center, terminates these interactions, thereby leading to the GDP-bound inactive state. Point mutations of key residues lead to a hydrolysis rate drop that keeps Ras in a GTP-bound active state. Now, high concentrations of active Ras have been associated to abnormal cell proliferation, emblematic of cancerous tissues dissemination. With this into consideration, the elucidation of Ras mechanisms for accelerating GTP cleavage appears as a major step in the development of cancer targeted therapies that would consist in restoring the hydrolysing capabilities within oncogenic Ras to a wild-type rate. In an attempt to gain insight into Ras catalysing properties at the atomic level, unconstrained Molecular Dynamics (MD) simulations describing the G domain at different levels of theory (Molecular Mechanics (MM), Semi-empirical and Density Functional Theory (DFT)) were carried out for NRas member in its wild-type and Gln 61 mutated forms. These simulations were coupled to biomechanic characterisations of the complexes under inspection employing the static modes approach. The latter method, allows the identification of hot spots {\it i.e.} responsive residues of the biomolecule, that have a mechanical influence on the GTPase function of the protein. Hence, they could serve as suitable sites to host drug-like molecules containing specific chemical groups that would facilitate GTP hydrolysis. The obtained results show that water molecules positioning is crucial for efficiently catalysing the reaction that takes place in NRas center. Indeed, the precise positioning observed within the wild-type is lost within the mutants studied here. Furthermore, the active site structural modifications undergone upon Gln 61 substitutions, together with solvent distribution in it, impact directly GTP electronic density. The latter is accommodated to a GDP-like state within the wild-type protein only, as experimentally determined in previous investigations. Thus, oncogenic Gln 61 mutations impair this major catalysing effect. Among three engineered NRas proteins of the Q61R mutated form, proposed during this thesis, one is presented during the defence while the three are described in the manuscript. The chemical groups inserted at the identified site enable the recovery of water distribution as within the wild-type. To end, during the defence only, an alternative reaction pathway of the enzymatic reaction is proposed
Cereto, Massagué Adrià. "Development of tools for in silico drug discovery." Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/454678.
Full textEl cribado virtual es un método quimioinformático que consiste en la criba de moléculas bioactivas de grandes bases de datos de moléculas pequeñas. Esto permite a los investigadores ahorrarse el coste de probar experimentalmente cientos o miles de compuestos candidatos, reduciéndolos hasta cantidades manejables. Para la validación de los métodos de cribado virtual hacen falta bibliotecas de moléculas señuelo. El software DecoyFinder fue desarrollado como aplicación gráfica de fácil uso para la construcción de bibliotecas de moléculas señuelo, y fue posteriormente ampliado con los hallazgos de investigación posterior sobre la construcción i rendimiento de bibliotecas de moléculas señuelo. El Protein Data Bank (PDB) es muy útil porque proporciona estructuras tridimensionales para complejos proteina-ligando, y por tanto, información sobre como interactúan. Para los métodos de cribado virtual que dependen de ellas, es extremadamente importante su fiabilidad. VHELIBS fue desarrollado como herramienta para inspeccionar e identificar, fácil e intuitivamente, las estructuras fiables del PDB, basándose en como de bueno es su encaje con sus correspondientes mapas de densidad electrónica. Mientras que el cribado virtual intenta encontrar nuevas moléculas bioactivas para determinadas dianas, el enfoque inverso también se utiliza: a partir de una molécula, buscar dianas donde presente actividad biológica no documentada. Este cribado inverso es conocido en inglés como “in silico target fishing”, o pesca de dianas “in silico”, y es especialmente útil en el ámbito de la reutilización de fármacos. Al comenzar esta tesis, no había ninguna plataforma de “target fishing” de libre acceso, y aunque durante los años se han desarrollado algunas, en todos los casos su predicción de bioactividad es cualitativa. Por eso se desarrolló una plataforma propia de “target fishing” de libre acceso, con la implementación de un nuevo método que proporciona la primera predicción cuantitativa de bioactividad para este tipo de plataforma.
Virtual screening is a cheminformatics method that consists of screening large small-molecule databases for bioactive molecules. This enables the researcher to avoid the cost of experimentally testing hundreds or thousands of compounds by reducing the number of candidate molecules to be tested to manageable numbers. For their validation, virtual screening approaches need decoy molecule libraries. DecoyFinder was developed as an easy to use graphical application for decoy library building, and later updated after some research into decoy library building and their performance when used for 2D similarity approaches. The Protein Data Bank (PDB) is very useful because it provides 3D structures for protein-ligand complexes and, therefore, information on how certain ligands bind and interact with their targets. For virtual screening apporaches relying on these structures, it is of the utmost importance that the data available on the PDB for the ligand and its binding site are reliable. VHELIBS was developed as a tool to easily and intuitively inspect and identify reliable PDB structures based on the goodness of fitting between ligands and binding sites and their corresponding electron density map. While virtual screening aims to find new bioactive molecules for certain targets, the opposite approach is also used: starting from a given molecule, to search for a biological target for which it presents previously undocumented bioactivity. This reverse screening is known as in silico or computational target fishing or reverse pharmacognosy, and it is specially useful for drug repurposing or repositioning. When this thesis was started, there were no freely available target fishing platforms, but some have been developed during the years. However, they are qualitative in the nature of their activity prediction, and thus we set out to develop a freely accessible target fishing web service implementing a novel method which provides the first quantitative activity prediction: Anglerfish.
Zhang, Jin. "In silico Identification of Thyroid Disrupting Chemicals : among industrial chemicals and household dust contaminants." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-125631.
Full textCastillo, Gonzalez Daimel. "Novel Quadruplex ligands : in silico and in vitro approaches." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22075/document.
Full textDNA and RNA G-rich sequences can adopt unusual arrangements that are known as G-quadruplexes (G4). The topologies and forms of these fascinating structures are very diverse. G4 are stabilized by the presence of monovalent cations and Hoogsteen Hydrogen bonds. Small molecules also contribute to the formation of stable forms mainly via π-π stacking interactions. Although G4s are known for decades, interest in this field started with their potential effect on inhibition of telomerase enzyme, a Reverse Transcriptase involved in the malignant transformation of most cancer cells. With regards to telomerase, cancer and G4, several groups have been involved in the discovery of new G4 stabilizers that would indirectly inhibit the enzyme. Most of the G4 ligands were identified following this paradigm. Hundreds of ligands have been identified during the past decade and this is still a very active field in science. Taking into account the advantages and easiness that offers the identification of new structures using computational techniques we built single and reproducible mathematical models with high screening capacity and low computational cost in order to use them on the identification of G4 ligands. With the use of QSAR modelling we can predict the telIC50 of a congeneric set of compounds. We have also been able to relate the molecular descriptors that appear in ours models with some structural features that scientific literature and SAR studies have reported in previous studies as appropriated for describing the above mentioned activity, also for congeneric set of ligands. Moreover, we built different models using non congeneric sets of compounds applying a consensus strategy and could identify six FDA approved ligands that stabilize G4 structures. Subsequently, by applying nonlinear techniques and a process for the cure of the database proposed for us in previous publications, we have performed a virtual screening of more than 500 000 ligands from a commercial database of compounds, followed of structure-based model in order to reduce the number of candidates. We were able to identify new ligands with stronger potency than the previous ones, which can also stabilize other G4 structures involved in processes related to cancer. These observations open a wide-ranging spectrum of possibilities to be explored. Despite the limitations of the QSAR modelling techniques explored along this work, we consider they can be combined and used carefully to address the search for new G4 stabilizers
Paz, Odailson Santos. "Triagem in silico e avalia??o in vitro de compostos antifalcizantes." Universidade Estadual de Feira de Santana, 2017. http://localhost:8080/tede/handle/tede/496.
Full textMade available in DSpace on 2017-08-08T21:31:24Z (GMT). No. of bitstreams: 1 TESE_Odailson Paz - com ficha.pdf: 4071411 bytes, checksum: 033f0c18eb721e7010e1ddd7ec27e10c (MD5) Previous issue date: 2017-05-25
Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Adenosine receptors are considered as potential targets for the development of drugs against different pathologies because they are involved in several physiological pathways. Due to the role of adenosine receptors of subtype 2B (RA2B) in the process of sickling cell, antagonists capable of blocking RA2B may be lead compounds for the development of new therapeutic alternatives to treatment of patients with sickle cell anemia. Then, the objective of this work was to identify anti-sickle cell agents capable of blocking RA2B activity. To achieve this goal, was built a pharmacophore model (model 04) capable of differentiating true ligands false-positive (area under the ROC curve = 0.94) and to classify RA2B antagonists, not used in the calibration of the model, regarding their Biological activities pKi = 7.5-9.3 (high potency), 5.5-7.4 (intermediate potency) and 5.4-4.0 (low potency). This pharmacophore model allowed the selection of 33 lead-like compounds from the ZINC database, between them12 compounds presented anti-sickle cell activity. In vitro cell assay with an agonist (NECA) and a RA2B antagonist (MRS1754), suggest that the anti-sickle cell activity is related to modulation of RA2B. Compounds Z1139491704 (pEC50= 7,77?0,17), Z168278894 (pEC50= 7,64?0,09) e Z847449186 (pEC50= 7,66?0,21) have anti-sickling activity Higher than MRS1754 (pEC50= 7,63?0,12) and do not present cytotoxic activity at micromolar range. In sum, it can be concluded that the in silico strategy used succeeded in identifying compounds with probable action antagonists of RA2B that can be considered as prototypes for the development of drugs useful in the treatment of patients with sickle cell anemia.
Os receptores de adenosina s?o considerados como alvos potenciais para o desenvolvimento de f?rmacos contra diferentes patologias por estarem envolvidos em diversas vias fisiol?gicas. Devido ao papel dos receptores de adenosina do subtipo 2B (RA2B) no processo de falciza??o de hem?cias, antagonistas capazes de bloquear RA2B podem ser compostos prot?tipos para o desenvolvimento de novas alternativas terap?uticas para o tratamento de pacientes com anemia falciforme.Diante desse cen?rio, o objetivo desse trabalho foi identificar agentes antifalcizantes capazes de antagonizar a atividade do RA2B. Para alcan?ar esse objetivo foi constru?do um modelo farmacof?rico (modelo 04 - 3 caracter?sticas aceptor e 1 doador de liga??o de hidrog?nio e 3 centros hidrof?bicos) que ? capaz de diferenciar ligantes verdadeiros de falso-positivos (?rea sob a curva ROC= 0,94)e classificar antagonistas de RA2B,n?o utilizados na calibra??o do modelo, quanto as suas atividades biol?gicas(pKi= 7,5-9,3 (alta pot?ncia), 5,5-7,4 (pot?ncia intermedi?ria) e 5,4-4,0 (baixa pot?ncia)). Esse modelo farmacof?rico permitiu a sele??o de 33 compostos lead like do banco de dados ZINC database para avalia??o biol?gica, dos quais 12 apresentaram atividade antifalcizante.Testes in vitro com um agonista (NECA) e um antagonista de RA2B (MRS1754), sugerem que a atividade antifalcizante est? relacionada a modula??o de RA2B.Os compostosZ1139491704(pEC50= 7,77?0,17),Z168278894 (pEC50= 7,64?0,09) e Z847449186 (pEC50= 7,66?0,21)possuem atividade antifalcizante superior ao MRS1754 (pEC50=7,63?0,12)e n?o apresentam atividade citot?xica em concentra??es micromolares. Dessa forma, pode-se concluir que a estrat?gia in silico utilizada logrou sucesso em identificar compostos com prov?vel a??o antagonistas de RA2B que podem ser considerados como prot?tipos para o desenvolvimento de f?rmacos ?teis no tratamento de pacientes com anemia falciforme.
Guillemain, Hélène. "Evaluation et application de méthodes de criblage in silico." Phd thesis, Conservatoire national des arts et metiers - CNAM, 2012. http://tel.archives-ouvertes.fr/tel-00814270.
Full textJun, Min Medical Sciences Faculty of Medicine UNSW. "Analysis of human cytomegalovirus susceptibility to novel antiviral agents." Publisher:University of New South Wales. Medical Sciences, 2008. http://handle.unsw.edu.au/1959.4/41443.
Full textUengwetwanit, Tanaporn [Verfasser], Wolfgang [Akademischer Betreuer] Sippl, Gabriele [Akademischer Betreuer] Costantino, and Gerhard [Akademischer Betreuer] Wolber. "In silico screening of inhibitors and conformational analysis of HCV NS5B polymerase / Tanaporn Uengwetwanit. Betreuer: Wolfgang Sippl ; Gabriele Costantino ; Gerhard Wolber." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2014. http://d-nb.info/1054636761/34.
Full textJorge, Daniel Macedo de Melo. "Busca In Silico de Inibidores de Fosfolipase A2 de Apis mellifera com validação In Vitro e In Vivo." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-21052014-094015/.
Full textApis mellifera is an insect belonging to the order Hymenoptera , Apidae family , has cosmopolitan occurrence and major ecological , economic, and medical . The hybrid subspecies that occur in Brazil have predominantly African features and came to be known as Africanized bees . The main characteristics of Africanized bees are aggressive behavior , good disease resistance, high honey production and increased frequency of enxameamentos , which has caused concern to be monitored , the increase in the number of accidents . The aggressiveness and increased frequency of exameamento cause they are repeatedly involved in massive human and animal attacks , making this kind of poisoning a problem of public health. The search for treatments for poisoning has been the subject of several studies . In general , treatments act on the effects caused by poison ( drug ), or the components of poison ( sera and inhibitors) . The main components of the venom are A2 ( PLA2 ) and phospholipase melittin . PLA2 is a major venom proteins , which degrades the plasma membrane of the cells and its effect is potentiated by the presence of melittin . The Apis mellifera PLA2 has determined the protein structure and active site identified . These characteristics qualify PLA2 as a potential target for drug design studies . The strategy for drug design aims to accelerate the identification of ligands , contributing to the process of drug discovery . This study aimed to identify in silico potential inhibitors of PLA2 Apis mellifera , in vitro and in vivo the potential inhibitory activity of selected compounds and identify the in vitro cytotoxicity of the compounds . The structure of PLA2 was obtained from the database (PDB ) and the search for compounds made from Maybridge Chembridge and libraries. The virtual screening was done with the aid of the GOLD program. The identified compounds ( 22 and 68 of the Maybridge Chembridge ) by GOLD programs were filtered with the use of computational tools for the selection of compounds with better interactions in the active site . The parameters used were as filters analyzes of chemical bonds and the fields of molecular interaction. The selected compounds ( 20 and 29 of the Maybridge Chembridge ) were submitted to a group of computer programs for the prediction of physico- chemical characteristics ( drug -like) , toxicity and biological activity of the ligands . The results of the predictions suggest that the compounds of Chembridge were used in experimental analysis . The compounds were obtained from Chembridge library (29 of 49 compounds). The compounds had their potential inhibitory activity evaluated in vitro and in vivo . The phospholipase activity was assessed for compounds 29 and 11 showed inhibitory activity against PLA2 . The 11 compounds were evaluated in vivo experiment with the induction of edema and 5 compounds were able to reduce edema . The compounds were evaluated for cytotoxicity that could cause . The in vitro cytotoxicity was calculated for three of the compounds obtained 5 inhibitors . The result of the experiment identified as cytotoxic compounds 2 and 1 with lower cytotoxicity . Despite the cytotoxicity identified , further studies should be conducted to determine the non-toxic inhibitory concentration . Therefore, the study identified 5 potential specific inhibitors of PLA2 Apis mellifera.
Lu, Pinyi. "Computational modeling-based discovery of novel classes of anti-inflammatory drugs that target lanthionine synthetase C-like protein 2." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/64370.
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Delfin, Dawn Athelsia. "A novel and potent antileishmanial agent in silico discovery, biological evaluation and analysis of its structure-activity relationships /." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1180527456.
Full textAnderson, E. "Screening of 7.5dpc mouse cDNA libraries by molecular indexing for genes involved in anterior patterning, and in silico analysis of a novel mouse protocadherin." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596096.
Full textBaccouche, Rym. "Conception de ligands protéiques artificiels par ingénierie moléculaire in silico." Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00807525.
Full textNicholas, Rudi Berto. "In silico and in vitro screening of marrubiin and marrubiin derivatives for antidiabetic activity on PTP1ß, C2C12 myocytes, chang liver hepatocytes and 3T3-L1 adipocytes." Thesis, Nelson Mandela Metropolitan University, 2013. http://hdl.handle.net/10948/d1020638.
Full textHeym, Peter Paul [Verfasser], Ludger A. [Akademischer Betreuer] Wessjohann, and Thomas E. [Akademischer Betreuer] Exner. "In silico characterisation of AtPARP1 and virtual screening for AtPARP inhibitors to increase resistance to abiotic stress / Peter Paul Heym ; Ludger A. Wessjohann, Thomas E. Exner." Halle, 2016. http://d-nb.info/1123998507/34.
Full textLagarde, Nathalie. "Méthodes de criblage virtuel in silico : importance de l’évaluation et application à la recherche de nouveaux inhibiteurs de l’interleukine 6." Thesis, Paris, CNAM, 2014. http://www.theses.fr/2015CNAM0943/document.
Full textVirtual screening is widely used in drug discovery processes.Structure selection in structure-based virtual screening methods is still problematic. We showed that simple and “low cost” binding site physico-chemical properties could be used to guide structure selection.The evaluation of virtual screening methods, necessary to ensure their reliability, relies on benchmarking databases quality. We created the NRLiSt BDB, gathering only manually curated data and taking into account ligands pharmacological profiles. A study using Surflex-Dock showed that the NRLiSt BDB should become the reference, both for the evaluation of virtual screening methods and for the identification of new ligands of the nuclear receptors.The use of a in silico/invitro hierarchical approach screening allowed to identify new IL-6 inhibitors, that could be used in rheumatoid arthritis treatment. In vitro results should be confirmed in vivo
Asses, Yasmine. "Conception par modélisation et criblage in silico d'inhibiteurs du récepteur c-Met." Phd thesis, Université Henri Poincaré - Nancy I, 2011. http://tel.archives-ouvertes.fr/tel-00653609.
Full textSayed, Ahmed Ahmed Mohamed Abdelaziz [Verfasser], Karl-Werner [Akademischer Betreuer] [Gutachter] Schramm, and Hans-Werner [Gutachter] Mewes. "In silico modeling using in vitro high throughput screening data for toxicity prediction within REACH / Ahmed Mohamed Abdelaziz Sayed Ahmed ; Gutachter: Karl-Werner Schramm, Hans-Werner Mewes ; Betreuer: Karl-Werner Schramm." München : Universitätsbibliothek der TU München, 2016. http://d-nb.info/1123729247/34.
Full textRenault, Nicolas. "Etude structurale in silico des récepteurs couplés aux protéines G appliquée au criblage virtuel de ligands mélatoninergiques, sérotoninergiques et cannabinergiques." Thesis, Lille 2, 2010. http://www.theses.fr/2010LIL2S060.
Full textIdentified as highly relevant therapeutical targets, the MT, and MT2 melatonin receptors, the5-HT2C serotonin and the CB2 cannabinoid receptors, which belong to the rhodopsin-like G proteincoupledreceptors (GPCRs) subfamily, have been studied by in silico approaches in order to identifycritical structural features for the binding, the selectivity and the pharmacological activity of theirligands. Gaining by sottie recent crystallographic data, various conformational states of these fourreceptors have been modeled according to the expected pharmacological profile. The comparativestudy of these various conformational states by molecular dynamics simulations has led to emphasizethe crucial rôle of the E2 extracellular loop and hélix 6 in the activation mechanisms of these GPCRs.On the basis of chemoinformatic methods, the virtual ligand screening targeting these threedimensionalmodels has promoted the characterization of a 5-HT2C receptor model able to bindspecifically inverse agonist ligands and the identification of pharmacological hits targeting the MTiand CB2 receptors
Blaise, Emilie. "Contribution à l'étude chimique et pharmacochimique de dérivés mono- bi- et tricycliques de pyridazines." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAF018/document.
Full textDYRK1A protein kinase belongs to the CMGC group and is involved in neurodegenerative disorders such as Alzheimer’s disease.In this context we examined an imidazo[1,2-B]pyridazine hit identified by biological screening, through detailed structure-Activity relationship studies. This compound was used to synthesize DYRK1A ATP-Competitive inhibitors by using metallo-Catalyzed methodologies (Pd, Cu) in order to introduce various functionalized moieties.Out of the 60 derivatives synthesized, 7 compounds showed nanomolar activities (IC50 = 41-130 nM).Beside this work of medicinal chemistry, new synthetic methodologies has been developed to regioselectively access polysubstituted pyridazine derivatives. Finally, we developed data and concepts to establish virtual pyridazine libraries for in silico screening
Camara, Ramatoulie. "Design, synthesis and biological evaluation of potential inhibitors of S100P, a protein implicated in pancreatic cancer." Thesis, University of Hertfordshire, 2015. http://hdl.handle.net/2299/17117.
Full textSpringett, Bradley Ross. "Design, synthesis and biological evaluation of inhibitors of polysialyltransferases PST and STX : design, synthesis and biological evaluation of a range of N-modified mannosamines, sialic acids and analogues from in silico screening as inhibitors of PolySia-NCAM biosynthesis with anti-migration activity." Thesis, University of Bradford, 2013. http://hdl.handle.net/10454/13528.
Full textSpringett, Bradley R. "Design, Synthesis and Biological Evaluation of Inhibitors of Polysialyltransferases PST and STX. Design, synthesis and biological evaluation of a range of N-modified mannosamines, sialic acids and analogues from in silico screening as inhibitors of PolySia-NCAM biosynthesis with anti-migration activity." Thesis, University of Bradford, 2013. http://hdl.handle.net/10454/13528.
Full textVillemagne, Baptiste. "Conception, synthèse et dévelopement d'inhibiteurs du répresseur transcriptionnel mycobactérien ETHR selon une approche par fragments. Une nouvelle approche dans la lutte contre la tuberculose." Thesis, Lille 2, 2012. http://www.theses.fr/2012LIL2S052/document.
Full textTuberculosis (TB) remains the leading cause of death due to a single infective agent with more than 1.5 million people killed each year. In 2011, the world health organization (WHO) estimated that one third of the world’s population is infected with Mycobacterium tuberculosis, the pathogen responsible for the disease. This phenomenon may be due to an explosive escalation of TB incidence that occurred in the 1980s due to the emergence of both resistant strains and HIV epidemic.In 2000, EthR, a mycobacterial transcriptional repressor, was identified as a key modulator of ethionamide (ETH) bioactivation. ETH is one of the main second-line drugs used to treat drug resistant strains. In 2009, it was shown that co-administration of ETH and drug-like inhibitors of EthR was able to boost ETH activity threefold in a mouse-model of TB-infection, thus validating the target for a new therapeutic strategy.This work deals with the discovery and optimisation of new EthR inhibitors, based on a small molecule, called a “fragment”, co-crystallized with the protein. We combined in silico screening, in vitro evaluation of the hit compounds, study of co-crystal structures and medicinal chemistry to develop three complementary approaches called “fragment growing”, “fragment merging” and “fragment linking” that led to the discovery of very potent inhibitors. Based on these results, we are currently selecting a potential candidate for new in vivo experiments
Goust, Victoire. "Fluorescent silica nanoparticles for multidimensional barcoding in droplets : towards high-throughput screening in two-phase microfluidics." Strasbourg, 2011. http://www.theses.fr/2011STRA6210.
Full textHigh-throughput screening has seen significant advances in the last 20 years. However, microtiter plate or microarray technologies are not optimal for all types of assays. Hence, implementation of droplet-based microfluidic platforms could bring a breakthrough in terms of throughput and reduction of costs. However, once out of the chip, droplets lose positional information to identify drop contents. It is thus necessary to label the encapsulated compounds. Since fluorescence is a common assay readout method, we opted for this strategy. The goal of this PhD was to produce a fluorescent material compatible with the specificities of droplet microfluidics, then to generate several optically encoded droplet libraries with it. We opted for silica nanoparticles (SNPs) covalently encapsulating organic fluorophores. We developed a novel synthesis route that enabled us to reach sizes down to 2. 5 nm, the smallest ever synthesized. The SNPs are brighter than starting fluorophores, better resist photobleaching and have tunable fluorescence polarization. Then, we studied the surface properties of these particles, especially their interaction with the surfactant. At long time scales, competition between particles and surfactant was shown. In addition, dramatic osmotic effects were highlighted in case of unequal particle concentration across droplets. Last, we investigated crucial parameters in fluorescent code design, then generated two-and three-color encoded droplet libraries. We also discussed optimizations and on-the-fly identification. We finally identify many applications would benefit from this encoding system
Mohan, Greeshma. "Silicone Elastomer-Based Combinatorial Biomaterial Gradients for High Throughput Screening of Cell-Substrate Interactions." Scholar Commons, 2015. http://scholarcommons.usf.edu/etd/5857.
Full textAmini, Nahid. "Novel Solid Phase Extraction and Mass Spectrometry Approaches to Multicomponent Analyses in Complex Matrices." Doctoral thesis, Stockholms universitet, Institutionen för analytisk kemi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-38625.
Full textKučera, Tomáš. "In silico screening inhibitotů SIRT6." Master's thesis, 2015. http://www.nusl.cz/ntk/nusl-332851.
Full textChen, Yi-Yun, and 陳依昀. "In silico drug screening for M2 macrophage repolarization to M1 macrophage." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/37722786831004547787.
Full textFüllbeck, Melanie [Verfasser]. "In-silico und In-vitro-Screening von Proteinliganden zur Apoptoseinduktion / von Melanie Füllbeck." 2007. http://d-nb.info/987586033/34.
Full textKuo, Yu-Lun, and 郭育倫. "In silico Therapeutic Drug Screening for Human Tumor based on the Gene Expression Profiles." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/54261737823983784297.
Full text國立臺灣大學
資訊工程學研究所
101
Drug development is an expensive and time-consuming process. Over the past two decades, the expense of drug development grows annually, but new drugs approved by FDA each year remain at less than 30. In order to reduce development time, we adopted the drug-repurposing strategy in combination with bioinformatics to discover new indications for old drugs. Connectivity Map (CMap) is a gene expression based in silico drug screening platform. Using disease signatures and drug expression profiles, CMap determines connections between disease and drug and predicts potential drugs by statistical methods. In this study, we employed several gene signatures to discover potential drugs for lung adenocarcinoma patients. In addition, we have validated the anticancer effects in lung cancer cells. By comparing the signature of effective drugs with those of lung adenocarcinoma patients, 89 differentially expressed genes were identified that produced a reverse signature. Furthermore, several lines of evidence show that cancer stem cells (CSCs) are associated with tumor initiation, disease relapse, and drug resistance. Therefore, we explored anti-cancer stem cell drugs by using embryonic stem cells (ESCs) and CSCs signature. We have identified trifluoperazine as an anti-lung CSC agent to inhibit tumor growth and overcome chemotherapy resistance. Moreover, we designed a drug combination prediction system using genetic algorithm. Based on the interaction of drug targets, we provided a systematic evaluation strategy for combinatorial drug therapy. We used the triple-negative breast cancer (TNBC) as our target disease for the prediction of possible drug combinations and discuss the effectiveness of the results by literature review. In the future, we will use experimental results to improve the prediction accuracy. Finally, Chinese herbal medicine (CHM) has become an important research field in the Ethnic Chinese community. Due to the lack of systematic scientific evidence and evaluation mechanism, there is a considerable challenge for performing quality assurance on CHM. We investigated quality consistency of CHM by using gene expression profiles and pathway analysis. Pathway analysis of PG2 shows that approximately 82% of the affected pathways are immune-related pathways. In addition, we discovered that PG2 enhances doxorubicin sensitivity in leukemia cancer cells.
VARDHARAKAN, THIYAGARAJAN, and THIYAGARAJAN VARDHARAKAN. "SCREENING AND VALIDATION OF NATURAL COMPOUNDS BY IN SILICO, IN VITRO, IN VIVO, AND NANOCARRIER." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/54914797151642333226.
Full text國立東華大學
生命科學系
103
Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine has been overexpressed in many types of tumors and plays an important role in number of cell signaling pathways including cell migration, proliferation, viability, and cell survival. This study was aimed to identify the novel and specific inhibitors from natural compounds via molecular docking of FAK (Y397) and investigate the underlying mechanism of action. The 3D structure of the FAK (PDB ID: 2AL6) was used for docking 107 Natural compounds. Based on their high affinity and energy interaction, top two compounds Antroquinonol from Antrodia camphorata and 16-hydroxy-cleroda-3,13-dien-16,15-olide (HCD) from Polyalthia longifolia were selected and further validated with C6 Glioma and N18 Neuroblastoma cell lines. Protein (2AL6) - ligands interaction analysis indicated that H-bond with residues Arg 86 and Arg 125. These compounds showed a potential effect on cell viability by MTT assay; in contrast cell cycle analysis showed cell arrest in subG1 and G0-G1 phase, respectively and further induction of apoptosis was confirmed by TUNEL assay. Atomic Force Microscopy data depicted that the formation of filopodia on intracellular surface decreased in treated cells as compared to the control. In addition, both compounds inhibited the activity of MMP 2 and 9 using Zymography. The protein levels of FAK, pFAK, Rac1 and cdc 42 were decreased, which are the key regulators for the formation of filopodia and cell migration. Further, both the compounds regulate the expression of epithelial mesenchymal transition (EMT) proteins. HCD and antroquinonol induce the autophagy through ROS mechanism. Further, HCD conjugated with Cu-MSN showed a controlled drug release and reduced the tumor growth of glioma. Taken together, this study suggests that Antroquinonol and 16-hydroxy-cleroda-3,13-dine-16,15-olide could be a potential inhibitor of FAK for anti-tumorigenesis and anti-metastasis.
Nguyen, Hoang-Chinh, and 阮皇章. "In Silico Screening and Experimental Evaluation of Small Molecule Inhibitors Against HCV NS3/4A Protease." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/50916225222839705966.
Full text中國文化大學
生物科技研究所
103
Hepatitis C virus (HCV) is the major cause of chronic liver diseases, including cirrhosis, liver failure, and liver cancer with over 170 million infected people worldwide. There is not any vaccine available for HCV treatment. NS3/4A serine protease is essential for viral replication, which shows a promising drug target for developing direct-acting anti-HCV agents. In this study, 150,000 small molecule compounds were extracted from chemical library and screened against NS3/4A protease by structure-based virtual screening (PyRx sofware). Ten compounds with the highest binding affinity were selected and used to evaluate their inhibitory activity by enzyme assay. The NS3/4A protease used for inhibitory kinetic analyses was the recombinant core enzyme, NS3-GSGS-NS4A. Among 10 selected compounds, compound 1 showed the highest inhibitory activity against the NS3/4A protease with IC50 and Ki values of 2.17 μM and 0.92 μM, respectively. Compound 1 was found to be a competitive inhibitor supposed to bind directly to the protease active site. In comparison with the control, the inhibitory activity of compound 1 was two-fold higher than that of hexapeptide, DEMEEC. Our newly identified compound 1 showed a promising anti-HCV agent for further drug development. These data suggested that virtual screening by means of molecular docking may an alternative way in drug discovery and development, which could save time, reduce chemical usage and find candidates efficiently.
Salentin, Sebastian. "In Silico Identification of Novel Cancer Drugs with 3D Interaction Profiling." Doctoral thesis, 2017. https://tud.qucosa.de/id/qucosa%3A30374.
Full textHuang, Shan-Han, and 黃聖翰. "Evaluation of hepatotoxic potential of the active compounds in traditional Chinese medicines by in silico screening." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/34710732209014303917.
Full text高雄醫學大學
藥學研究所
101
The perception that natural substances are deemed safe has made traditional Chinese medicine (TCM) gain popularity in the treatment and prevention of disease globally. However, such an assumption is often misleading for lack of scientific validation. To assess the safety of TCM, the in silico screening provides major advantages over the classical laboratory approaches in resource- and time-saving and full reproducibility. To screen the hepatotoxic potential of the active compounds of TCM, a quantitative structure-activity relationship model was firstly established by utilizing chemicals from the Liver Toxicity Knowledge Base. These chemicals were annotated with drug-induced liver injury information obtained from clinical trials and post-marketing surveillance. The performances of nested 10-fold cross-validation were 79.1%, 91.2%, and 53.8% for accuracy, sensitivity, and specificity, respectively. The external validation on 84 known hepatotoxic ingredients of common herbal medicines yielded a high accuracy (92.8%). After screening the TCM Database@Taiwan, the world’s largest TCM database, a total of 6853 (21.4%) ingredients were predicted with hepatotoxic potential. One hundred chemicals predicted with highest hepatotoxic potential by our model were further verified by published literatures. Our study indicates this model can serve as a complementary tool to evaluate the safety of TCM.
Barbas, R., M. Font-Bardia, Anant R. Paradkar, C. A. Hunter, and R. Prohens. "Combined virtual/experimental multicomponent solid forms screening of sildenafil: new salts, cocrystals, and hybrid salt-cocrystals." 2018. http://hdl.handle.net/10454/16663.
Full textNew multicomponent solid forms of sildenafil have been discovered by means of a combined virtual/experimental cocrystal screening. Coformer selection of candidates was conducted based on an in silico screening method from a database of more than 2000 organic compounds, and the intensive experimental screen produced 23 new solid forms. Since the 12 coformers chosen have a combination of phenol and carboxylic acid groups, a variety of cocrystals, salts, and hybrid salt-cocrystals were discovered and characterized.
"Functional Study of the N-terminal of Influenza B Nucleoprotein and In-silico Screening of Inhibitors Targeting Influenza Polymerase." 2016. http://repository.lib.cuhk.edu.hk/en/item/cuhk-1292522.
Full textCoelho, Inês Cristina Ferreira. "Combining metric and vector space data mining methods for screening CFTR rescuers in cystic fibrosis." Master's thesis, 2017. http://hdl.handle.net/10451/30865.
Full textO objetivo principal desta dissertação é desenvolver modelos para propor moléculas de interesse que podem se tornar em princípios ativos no tratamento da fibrose quística. Neste projeto apresenta-se uma abordagem in silico para a seleção de moléculas que possivelmente têm capacidades terapêuticas em relação à fibrose quística. Este processo é efetuado computacionalmente com a utilização de ferramentas de prospeção de dados e os objetivos primordiais deste processo são a identificação e seleção de moléculas que podem ajudar no combate à doença para posterior teste em laboratório. Para este efeito foram desenvolvidos previsões para a capacidade terapêutica das moléculas em dois espaços: i) espaço vetorial; ii) espaço métrico. No espaço vetorial as previsões foram realizadas tendo em conta os descritores moleculares das moléculas, com recurso ao método estatístico e computacional random forest. As moléculas foram também representadas num espaço métrico construído com a dissemelhança molecular entre as mesmas, onde ocorreu uma redução de dimensões tornando possível a representação das instâncias num plano bidimensional – este espaço métrico foi subsequentemente analisado por uma ferramenta estatística denominada kriging. Para comprovar os métodos escolhidos, usaram-se dois conjuntos de dados; potenciadores e ativadores de anoctaminas (moléculas de possível interesse para o tratamento da fibrose quística) e corretores da proteína causadora da fibrose quística (CFTR - Cystic fibrosis transmembrane conductance regulator ). No âmbito desta dissertação, foram identificadas 10 moléculas provenientes do estudo com potenciadores de anoctaminas e 18 moléculas provenientes do estudo com corretores da CFTR, para serem testadas em laboratório. Adicionalmente, foram recolhidos dados de repositórios de informação biológica para validar os métodos utilizados. Este passo adicional permite concluir que algumas das moléculas escolhidas têm ligações diretas e indiretas à fibrose quística, dando credibilidade ao método desenvolvido. É importante referir que a forma como este projeto foi desenvolvido permite a utilização de diferentes conjuntos de dados de ligandos para proteínas alvo, o que torna este método flexível e adaptável à doença que seja objeto de estudo.
The main goal of this dissertation is to develop models in order to identify and propose lead chemical molecules that can possibly become principal actives against the cystic fibrosis disease. In this project it is presented an in silico approach to perform a molecular screening on possible therapeutic candidates for the cystic fibrosis disease. This process is done computationally with data mining tools and the main objectives are the identification and selection of molecules to further testing in the laboratory. To achieve this goal the data mining exercise was developed on two spaces: i) vectorial space, ii) metric space. On the vectorial space, molecular descriptors were selected to implement a random forest algorithm (a supervised machine learning method) in order to realize forecasts on the molecule ability to treat the disease. The studied molecules were also represented in a metric space that was developed using molecular dissimilarity between all molecules. This dissimilarity values were modelled to fit in a 2 dimensional representation - In this metric space the statistical tool chosen was kriging. To prove the chosen methodology, two main datasets were used: A dataset with Anoctamin activators or potentiators (molecules of interest to treat the cystic fibrosis disease) and a dataset with correctors of the protein which causes cystic fibrosis (CFTR - Cystic fibrosis transmembrane conductance regulator). Based on these datasets, 10 and 18 molecules were selected respectively to be further tested in a lab environment. To conclude the work and validate the workflow results, an additional analysis was performed using selected information repositories. This additional step has confirmed that some of the chosen molecules are directly and indirectly related to cystic fibrosis, giving some credibility to the proposed method. Finally, the way this project was developed enables the use of different datasets with ligands of the target proteins as input, making the method flexible and adaptable to any disease in study.
Shih, Kuei-Chung, and 石貴中. "Develop 3D-QSAR Combination Modeling Approach for Screening and Optimizing Target Protein Inhibitors Based on Pharmacophore, CoMFA, and CoMSIA in Silico." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/71384727992471716894.
Full text國立清華大學
資訊工程學系
99
Quantitative Structure Activity Relationships (QSAR) is an important technique in the rational drug design, which was used to build computational models to find a statistically significant correlation between the receptor and inhibitors. There are two mainstream of 3D-QSAR technologies, namely Comparative Molecular Field Analysis (CoMFA)/ Comparative Molecular Similarity Index Analysis (CoMSIA) and Pharmacophore. Most significant function of pharamcophore model is to use 3D screen to recognize the related target protein inhibitors. However, the number of pharmacophore features was restricted as five chemical features at maximum, and which could not describe the 3D space limitation of the binding site. This restriction induces incompletely describing the chemical features of inhibitors. Contrastingly, the other two models, CoMFA and CoMSIA were not suitable to search 3D databases, but can easily be used to modify the molecule structure optimization and describe the limit range of molecule weights. Additional, CoMFA and CoMSIA models use contours to describe the chemical features of inhibitor. The number of contours was not restricted, that could reflect the chemical features of inhibitor. Therefore, CoMFA and CoMSIA models could provide better predication ability to predict the bioactivity. According to above characters, we prefer to combine these two different technologies. We propose a 3D-QSAR combination modeling approach to solve two 3D-QSAR technical shortcomings of each other. Our combination approach could provide a valuable tool in the design of new leads with desired biological activity by virtual screening.
Liu, Ping-Jung, and 劉蘋瑢. "Screening of various peptide sequences of food proteins for their potential as prolyl endopeptidase inhibitor and evaluation of the correlation between in silico and in vitro analyses." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/p978va.
Full textSantos, Carolina Maria Duarte. "A evolução das estratégias do design racional de fármacos." Master's thesis, 2013. http://hdl.handle.net/10400.26/14113.
Full textO desenho de novos fármacos é um processo longo e demorado, que envolve várias etapas, tais como, a fase de descoberta da molécula, as fases de desenvolvimento, onde se realizam os ensaios pré-clínicos em animais e os ensaios clínicos em seres humanos, a fase de registo e em caso de aprovação do fármaco, a sua comercialização para o mercado. Na fase clínica do desenvolvimento dos fármacos, pretende-se obter informações sobre a segurança e eficácia do fármaco, como também, sobre outras variáveis, tais como por exemplo, as propriedades farmacocinéticas e a sua toxicidade. A descoberta e o desenvolvimento de novos fármacos é efetuado segundo várias abordagens, estando estas a serem estudadas e melhoradas no decorrer dos anos, para que se obtenham novos fármacos, através de metodologias facilmente executáveis, eficientes e economicamente rentáveis. Assim, relativamente ao desenho de novos fármacos, introduziu-se na indústria farmacêutica, um novo modelo de abordagem, o modelo in silico. Este diferencia-se dos modelos in vivo e in vitro, dado que utiliza metodologias computacionais para a descoberta de novos fármacos. Desta forma, foi através da introdução do software computacional que possibilitou aos investigadores analisarem vários compostos ao mesmo tempo. Para essa análise, foi necessário a utilização de uma técnica que conseguisse avaliar rapidamente inúmeros compostos ao mesmo tempo. Desta maneira, surgiu o screening de alto rendimento (HTS). Apesar da sua eficiência, é necessário que as indústrias farmacêuticas obtenham o seu equipamento, que ao nível económico é uma grande desvantagem para as empresas. Assim, e em alternativa ao HTS, desenvolveu-se uma nova abordagem, o desenho de fármacos baseado em fragmentos (FDBB). Esta metodologia têm vindo a ser muito utilizada pelas indústrias farmacêuticas na descoberta de novos fármacos e um exemplo disso mesmo, foi a descoberta em 2011 do primeiro fármaco, o vemurafenib. Este é utilizado no tratamento do mieloma metastático.
FENG, CHIEN-JUI, and 馮芊瑞. "Screening of IC Silicon Wafer Manufacturing Parameter by Conducting MTS." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/35826051201784355461.
Full text中華大學
企業管理學系碩士班
102
The lifecycle of electronic product becomes shorter in recent years, therefore, it is necessary to seek for a faster proactive test for semiconductor material to shorten the test lifecycle in order to achieve comprehensive production. As a consequence, it creates a product with a price advantage with high yield and reduce costs. In addition to actively innovate technologies and develop superior quality of material, it is indispensable to master the product quality. With the rising demand of customer s for high quality, the current manufacturing process or processing are using large amount of parameters to cross exam with the product as basis for quality determination. However, when there are increasing number of parameters which are to monitor variation, the efficiency of quality control system which storage data, analysis statistic data and determinate the result, begins slowing down. This leads to increasing cost of quality parameter analysis and testing. Testing manufacturing engineering plays a very important role in the silicon wafer manufacturing process. It is not only a huge investment on the initial production equipment, but also the number and cost of following up testers occupy relatively huge amount of human resources in the entire production. This study aim to screen the parameters by conducting MTS on the purpose to minimize the silicon wafer product testing items. Furthermore, it undergoes an experiment to confirm the efficiency of the determinate important characteristic variable is efficiency. As a result, it can provide a competitive testing process. The case study is base on the variation testing database of a company after wafer grinding, dicing and cleaning of 300mm(12 inches) single crystal silicon. The result shows that (1)MTSis able to efficiently distinguish main manufacturing parameter and secondary manufacturing parameter. (2)Taguchi experiment design can efficiently reduce number of experiment of multiple variable.