Дисертації з теми "Moleculor Biophysics"
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Huang, Po-Ssu Rees Douglas C. "Biochemistry and molecular biophysics /." Diss., Pasadena, Calif. : California Institute of Technology, 2004. http://resolver.caltech.edu/CaltechETD:etd-06012004-214823.
Повний текст джерелаTeng, Ching-Ling. "Mapping molecular accessibility and intermolecular interactions between ribonuclease A and paramagnetic small molecules using nuclear magnetic relaxation /." Full text, Acrobat Reader required, 2002. http://viva.lib.virginia.edu/etd/diss/ArtsSci/Biophysics/2002/Teng/TengDiss.pdf.
Повний текст джерелаElmlund, Hans. "Protein structure dynamics and interplay : by single-particle electron microscopy." Doctoral thesis, Stockholm : Teknik och hälsa, Technology and Health, Kungliga Tekniska högskolan, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4669.
Повний текст джерелаNeetz, Manuel. "Collective behavior of molecular motors." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-85935.
Повний текст джерелаShen, Tongye. "Fluctuations and stochastic dynamics in molecular biophysics /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2002. http://wwwlib.umi.com/cr/ucsd/fullcit?p3061634.
Повний текст джерелаMukund, Shreyas Ram. "Single molecule biophysics of homologous recombination." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708842.
Повний текст джерелаTang, Ming. "Atomic-scale biophysics modelling of type I collagen in the extracellular matrix." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/124650/1/Ming_Tang_Thesis.pdf.
Повний текст джерелаKlingelhoefer, Jochen W. "Biophysics of nanopores-multiscale molecular dynamics simulation studies." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.540136.
Повний текст джерелаBellaiche, Mathias Moussine Jacques. "Molecular mechanisms of protein self-assembly and aggregation." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/277621.
Повний текст джерелаKing, Paul M. "Application of free energy perturbation calculations to molecular biophysics." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257951.
Повний текст джерелаBondar, Ana-Nicoleta [Verfasser]. "Computational Molecular Biophysics of Membrane Reactions / Ana-Nicoleta Bondar." Berlin : Freie Universität Berlin, 2020. http://d-nb.info/121464144X/34.
Повний текст джерелаKoga, Daniel Inoue [UNESP]. "Análise vibracional do α-tocoferol". Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/87501.
Повний текст джерелаConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
O α-tocoferol é a principal dentre as moléculas que desempenham o papel biológico de vitamina E, sendo a que apresenta maior biodisponibilidade e atividade. Além dos papéis como vitamina, o α-tocoferol tem diversas funções no organismo incluindo a inibição de proteínas da família PLA2. Esse trabalho apresenta a análise vibracional do α-tocoferol inteiro no vácuo seguido pela otimização geométrica da molécula em ambiente protéico. O estudo do tocoferol no vácuo foi realizado dentro do formalismo do DFT usando o funcional de correlação-troca B3LYP e a base de funções 6-311G**. A análise vibracional foi realizada em um programa desenvolvido pelo autor. Em ambiente protéico, o processo foi dividido em duas etapas: a otimização geométrica do sistema inteiro no formalismo da dinâmica molecular e a otimização somente do ligante e de um envelope protéico em DFT. Por dificuldades computacionais não foi possível a análise vibracional do sistema.
The α-tocopherol is the most important molecule which has the biological role of vitamin E, having the greatest biodisponibility and activity. Besides its vitamin roles, the α- tocopherol has many functions in organisms including the inhibition of proteins of the PLA2 family. This work presents the vibrational analysis of the whole α-tocoferol in vacuum followed by the geometric optimization of the molecule in protein environment. The study of tocopherol in vacuum was done in the DFT framework using the B3LYP exchangecorrelation functional with the 6-311G** function basis and the vibrational analysis was done by a program developed by the author. The process was divided in two steps for the study in protein environment: the geometrical optimization of the whole system in the molecular dynamics framework and the optimization of the ligand and a protein envelope in DFT. Due to computational troubles it was not possible to perform the vibrational analysis of this system.
Harrison, Ryan M. "Molecular biophysics of strong DNA bending and the RecQ DNA helicase." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:f02fc167-b705-4275-a413-21d13b5d94c3.
Повний текст джерелаElnatan, Daniel. "Asymmetric Mechanism of Molecular Chaperone Hsp90." Thesis, University of California, San Francisco, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10690095.
Повний текст джерелаHsp90 is a highly conserved, ATP-dependent molecular chaperone that is essential for maintaining the functions of its client proteins. It has been estimated that about 10% of the proteome of a eukaryotic cell interacts with Hsp90. A large subset of this portion consists of protein kinases and steroid hormone receptors, putting Hsp90 as the master regulator of many essential cellular functions. The mechanism of how Hsp90 uses ATP hydrolysis to carry out its function remains unclear. Structural studies of Hsp90 revealed that Hsp90 is a V-shaped homodimer with each protomer composed of three well-folded domains: an ATP-binding N-terminal Domain (NTD), a Middle Domain (MD), and a C-terminal dimerization Domain (CTD). Efficient ATP hydrolysis by Hsp90 requires that the dimer forms a closed state where NTDs are dimerized, forming a closed ”clamp” conformation that is stabilized by ATP binding. The kinetics of forming this stably closed state is not driven by ATP binding, as there are other rate-limiting steps that need to occur within the protein to allow the NTDs to be dimerized. So how does Hsp90 actually use the energy from ATP to remodel its client protein? the focus of this thesis examines the other possibility of this happening during ATP hydrolysis. In the first chapter, I followed up an observation made by a previous graduate student Laura Lavery. She observed that the ATP-bound closed state of a mitochondrial Hsp90 (TRAP1) is asymmetric. The asymmetry is most prominent at the juncture between the MD:CTD interface—one protomer is buckled while the other remains straight, resembling the same conformation previously observed in the symmetric closed ”clamp” state. This buckling happens precisely where conserved binding sites have been mapped for client proteins. This suggests that if conformational changes were to occur due to ATP hydrolysis, subsequent rearrangements of the asymmetric MD:CTD interfaces back to the previously observed symmetric closed state vii could be used to drive client protein remodeling. Using a combination of biophysical methods (crystallography, Double Electron-Electron Resonance (DEER), and FRET), we observed that TRAP1 hydrolyzes the 2 bound ATPs sequentially. The buckled protomer hydrolyzes the first ATP, which is then followed by a flip in the asymmetry (the buckled conformation becomes straight and vice versa, on each side), which primes the second ATP for hydrolysis by a buckled protomer. In this model, the MD:CTD interface is guaranteed to undergo remodeling with each ATP hydrolysis and would make efficient use of energy from ATP. The implications for this asymmetric ATP hydrolysis mechanism may also be relevant to other Hsp90s. While we have not observed any other asymmetric Hsp90 structures by itself, several functional Hsp90 complexes seen so far seem to have asymmetric composition/arrangements of their components. In the second chapter, we explore how TRAP1 ATPase activity can be modulated by different divalent cations as co-factors. Despite having two ATP binding sites, the ATPase activity of most Hsp90 homologs appears to be non-cooperative (each site behaves independently from one another). However, we saw that ATPase activity of TRAP1 can be cooperative in presence of calcium, and the activity in presence of magnesium appears to be bi-phasic, with higher activity at low ATP concentrations. This unique behavior of TRAP1 may yet be another adaptation of the Hsp90 machine that has evolved within the mitochondrial matrix environment. Using crystallography, we also discovered that calcium binds to the NTD of TRAP1 unlike previously observed chaperone/calcium/ATP complexes. While the exact biological role for this phenomena is not yet clear, these findings provide a clear molecular basis for the regulation of TRAP1 by calcium. Taken together, the work described in this thesis provide insights into the mechanism of ATP hydrolysis by Hsp90, and a potential role that TRAP1 plays in calcium/magnesium-regulated mitochondrial physiology.
Cabeza, de Vaca López Israel. "Mapping biophysics through enhanced Monte Carlo techniques." Doctoral thesis, Universitat Politècnica de Catalunya, 2015. http://hdl.handle.net/10803/334172.
Повний текст джерелаAquesta tesi es centra en l'estudi de les interaccions moleculars amb detall atomic i es divideix en un capítol d'introducció i quatre capítols que fan referència a diferents problemes i enfocaments metodològics. Tots ells se centren en el desenvolupament i millora dels algoritmes computacionals de Monte Carlo per estudiar, de manera eficient, el comportament d'aquests sistemes a un nivell mecànica molecular clàssica. Els quatre problemes biofísics estudiats en aquesta tesi són: acoblament induït entre la proteïna-lligand i entre DNA-lligant per comprendre el mecanisme d'unió, resposta de les proteïnes a l'estirament, i la generació/puntuació d'acoblament entre poses proteïna-proteïna. La tesi s'organitza de la següent manera: El primer capítol correspon a l'estat de l'art en mètodes computacionals per estudiar les interaccions biofísiques, que és el punt de partida d'aquesta tesi. El nostre PELE algoritme i els principals mètodes estàndard com ara la dinàmica molecular s'explicaran en detall. El capítol dos es centra en les principals modificacions PELE per afegir noves característiques, com ara l'addició d'un nou camp de força, solvent implícit i modes normals per aquests estudis de simulació d'ADN. Es fa un estudi, comparació i validació de les conformacions generades per sis fragments d'ADN representatius amb PELE utilitzant dinàmica molecular com a referència. El tercer capítol està dedicat a l'aplicació dels nous mètodes implementats i provats en PELE per estudiar les interaccions proteïna-lligand i la interacció lligand-DNA utilitzant quatre sistemes. En primer lloc, se estudia la unió a proteïnes GUN4 combinant PELE i simulacions de dinàmica molecular. A més, es proposa un acoblament que ha sigut corroborat per una nova estructura cristal·lina publicada durant el procés de revisió de l'estudi mostrant l'exactitud de les nostres prediccions. En el segon projecte, hem utilitzat la nostra versió millorada de PELE per generar el primer model estructural d'una glucosa alfa substrat 1,6-bisfosfat unit a la fosfomanomutasa humana 2, que demostra que aquest lligant pot adoptar dues orientacions de baiza energia. El tercer projecte és l'estudi de les interaccions d'ADN lligant per tres medicaments cisplatí on se avalua l'energia lliure d'unió utilitzant Markov States Models. Es mostren excel·lents resultats respecte d'altres mètodes d'energia lliure estudiats amb dinàmica molecular. L'últim projecte és l'estudi de l'intercalador d'ADN anomenat daunomicina on es simula i estudia el procés d'unió amb PELE. El capítol 4 es centra en l'estudi computacional dels perfils d'extensió de la força durant el desplegament de la proteïna. Hem afegit una restricció harmònica dinàmica seguint un procediment similar al aplicat en dinàmica molecular en el nostre algoritme Monte Carlo per fixar o moure alguns àtoms seleccionats obligant a desplegar la proteïna en una direcció definida. Aquesta tècnica s'ha implementat i comparat amb dinàmica molecular per les proteïnes ubiquitina i azurin. D'altra banda, hem afegit aquesta modificació a un algoritme ben conegut anomenat MCPRO del grup de William Jorgensen a la Universitat de Yale per avaluar l'energia lliure associada al desplegament del sistema deca alanina. El capítol cinc correspon a la introducció d'un enfocament multiescala per estudiar l'acoblament proteïna-proteïna. Un model de gra gruixut es combinat amb una exploració Monte Carlo per reduir els graus de llibertat i generar milers de poses proteïna-proteïna d'una manera ràpida. Les poses produides per aquest procediment es perfeccionan i evaluan a través d'una protonació, optimització d'enllaços d'hidrogen, i minimització a escala atòmica per identificar les millors poses. Es presenten dos casos de prova on s'ha aplicat aquest procediment que mostra una bona precisió en les prediccions: tryptogalinin i ferredoxina / flavodoxina systems.
Le, Tung T. "Single-molecule biophysics of DNA bending: looping and unlooping." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/53979.
Повний текст джерелаKoussa, Mounir Ahmad. "The Biophysics of Vertebrate Hearing: A Single-Molecule Approach." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467499.
Повний текст джерелаMedical Sciences
Tesdahl, Natalya S. "Molecular basis of autism-like behavior in SAPAP3-deficient mice." Thesis, University of Iowa, 2017. https://ir.uiowa.edu/etd/5657.
Повний текст джерелаGoryaynov, Alexander G. "Molecular Size and Charge Effects on Nucleocytoplasmic Transport Studied By Single-Molecule Microscopy." Bowling Green State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1357278635.
Повний текст джерелаJones, Nathan Jones. "Single Molecule Analysis of DNA Interactions." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1511959163350735.
Повний текст джерелаAdcock, Charlotte. "Molecular modelling and electrostatic properties of ion channels." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297941.
Повний текст джерелаRoman, Horia Nicolae. "Smooth muscle molecular mechanics in the latch-state." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121358.
Повний текст джерелаLe muscle lisse possède la capacité unique de maintenir une force élevée tout en consommant peu d'adénosine triphosphate (ATP); cette propriété est appelée 'latch-state'. La théorie la mieux connue pour expliquer cet état suggère que si la myosine est désactivée (déphosphorylation de sa chaîne légère) pendant qu'elle est attachée à l'actine, elle reste attachée et maintient la force. D'autres théories suggèrent que la myosine désactivée et détachée peut s'attacher à l'actine pour maintenir la force et que les protéines régulatrices de l'actine participent aussi à cet effort. Toutes les théories sur l'état 'latch' ont été extrapolées à partir de mesures réalisées sur la totalité du muscle sans jamais être confirmées au niveau moléculaire. Le but principal de cette thèse était de vérifier les théories de l'état 'latch' au niveau moléculaire. Afin de mieux comprendre l'état 'latch', le rôle de la calponine, dans l'attachement de la myosine non-phosphorylée à l'actine, a été déterminé. Des pinces optiques ont été utilisées pour mesurer la force moyenne de leur détachement (Funb) en l'absence et en présence de la calponine. La calponine a augmenté la Funb. La phosphorylation de la calponine avec l'enzyme protéine kinase II (Ca2+-calmoduline dépendante), qui a pour effet de détacher la calponine de l'actine, a diminué la Funb jusqu'au niveau de l'actine non-régulée. De plus, des mesures de force ont été réalisées à haute force ionique, détachant cette fois-ci la calponine de la myosine. Ceci a aussi diminué la Funb jusqu'au niveau de l'actine non-régulée. Ces résultats montrent que la calponine augmente la Funb de la myosine non-phosphorylée à l'actine par liaison croisée (myosine-calponine-actine). Ensuite, l'effet de la caldesmone sur la Funb a été étudié; la caldesmone augmente aussi la Funb. Puisque la tropomyosine est connue pour promouvoir les actions biochimiques et mécaniques de la caldesmone, son action sur la Funb en combinaison avec la caldesmone a aussi été mesurée. La tropomyosine augmente la Funb lorsqu'elle est seule mais n'a pas d'effet synergétique avec la caldesmone. La phosphorylation de la caldesmone avec la kinase régulatrice des signaux extracellulaires (ERK) a diminué la Funb en dessous du niveau de l'actine non-régulée. Ce dernier résultat suggère un mécanisme de relaxation à partir de l'état 'latch' étant donné que la phosphorylation de la caldesmone par ERK se produit tard dans la contraction. D'autre part, l'examen des traces de force a révélé un comportement viscoélastique de la myosine en présence de la caldesmone phosphorylée, ce qui semble soit prévenir l'attachement, soit promouvoir le détachement de l'actine, menant ainsi à la relaxation du muscle à partir de l'état 'latch'. Finalement, la démonstration ultime de l'état 'latch' au niveau moléculaire requiert la déphosphorylation de la myosine pendant les mesures de forces moléculaires faites à l'aide de pinces optiques. Cependant l'addition de la phosphatase de la chaîne légère de myosine ne peut se faire sans perturber les mesures de mécanique au niveau moléculaire. A cet effet, un appareil micro-fluidique a été conçu et développé pour permettre l'ajout de solutions biochimiques à la chambre de mesure de micromécanique sans créer de débit net. Des micro-canaux ont été créés par photolithographie sur substrats de silicium suivie d'un transfert des formes sur polymethylsiloxane (PDMS). La chambre des micro-canaux a ensuite été collée à une membrane de polycarbonate qui elle a ensuite été collée à la chambre de micromécanique. Les micro-canaux assurent la livraison rapide et uniforme tandis que la membrane assure le transfert efficace des produits biochimiques tout en empêchant un débit net. Le fonctionnement de l'appareil a été vérifié en injectant de l'ATP en présence d'actine et de myosine phosphorylée. La propulsion de l'actine par la myosine a été observée validant ainsi le principe de l'appareil microfluidique.
Cowe, H. J. de L. "Molecular studies of natural products and related compounds." Thesis, Robert Gordon University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370758.
Повний текст джерелаMarshall, John. "Molecular characteristics of the locust nicotinic acetylocholine receptor." Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315055.
Повний текст джерелаHanlon, Michael Richard. "Molecular modelling and biophysical characterisation of three proteins." Thesis, Birkbeck (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326154.
Повний текст джерелаSloutsky, Roman. "Mechanical Unfolding of Solvated α-synuclein Studied by Molecular Dynamics Simulations". The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1245435450.
Повний текст джерелаIshimaru, Hiroshi. "Molecular biology of novel glutamate receptors in Xenopus laevis." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309048.
Повний текст джерелаCrawford, Robert. "Single-molecule DNA sensors and cages for transcription factors in vitro and in vivo." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:dc51a40b-4236-48ad-850e-e7e0010a823c.
Повний текст джерелаKoga, Daniel Inoue. "Análise vibracional do α-tocoferol /". São José do Rio Preto : [s.n.], 2010. http://hdl.handle.net/11449/87501.
Повний текст джерелаBanca: José Roberto Ruggiero
Banca: Luis Paulo Barbour Scott
Resumo: O α-tocoferol é a principal dentre as moléculas que desempenham o papel biológico de vitamina E, sendo a que apresenta maior biodisponibilidade e atividade. Além dos papéis como vitamina, o α-tocoferol tem diversas funções no organismo incluindo a inibição de proteínas da família PLA2. Esse trabalho apresenta a análise vibracional do α-tocoferol inteiro no vácuo seguido pela otimização geométrica da molécula em ambiente protéico. O estudo do tocoferol no vácuo foi realizado dentro do formalismo do DFT usando o funcional de correlação-troca B3LYP e a base de funções 6-311G**. A análise vibracional foi realizada em um programa desenvolvido pelo autor. Em ambiente protéico, o processo foi dividido em duas etapas: a otimização geométrica do sistema inteiro no formalismo da dinâmica molecular e a otimização somente do ligante e de um envelope protéico em DFT. Por dificuldades computacionais não foi possível a análise vibracional do sistema.
Abstract: The α-tocopherol is the most important molecule which has the biological role of vitamin E, having the greatest biodisponibility and activity. Besides its vitamin roles, the α- tocopherol has many functions in organisms including the inhibition of proteins of the PLA2 family. This work presents the vibrational analysis of the whole α-tocoferol in vacuum followed by the geometric optimization of the molecule in protein environment. The study of tocopherol in vacuum was done in the DFT framework using the B3LYP exchangecorrelation functional with the 6-311G** function basis and the vibrational analysis was done by a program developed by the author. The process was divided in two steps for the study in protein environment: the geometrical optimization of the whole system in the molecular dynamics framework and the optimization of the ligand and a protein envelope in DFT. Due to computational troubles it was not possible to perform the vibrational analysis of this system.
Mestre
Stelzl, Lukas Sebastian. "Studying marcomolecular transitions by NMR and computer simulations." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:6e4bbe06-fc58-471b-a932-d940fe78b9a5.
Повний текст джерелаSamanta, Amrita. "Understanding the molecular mechanism of TRP channel activation/inhibition by structural analysis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1533499522272657.
Повний текст джерелаMudumbi, Krishna Chaitanya. "NUCLEAR ENVELOPE TRANSMEMBRANE PROTEIN DISTRIBUTION AND TRANSPORT STUDIED BY SINGLE-MOLECULE MICROSCOPY." Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/489984.
Повний текст джерелаPh.D.
The nucleus of eukaryotic cells is a vitally important organelle that sequesters the genetic information of the cell, and protects it with the help of two highly evolved structures, the nuclear envelope (NE) and nuclear pore complexes (NPCs). Together, these two structures mediate the bidirectional trafficking of molecules between the nucleus and cytoplasm by forming a barrier. NE transmembrane proteins (NETs) embedded in either the outer nuclear membrane (ONM) or the inner nuclear membrane (INM) play crucial roles in both nuclear structure and functions, including: genome architecture, epigenetics, transcription, splicing, DNA replication, nuclear structure, organization and positioning. Furthermore, numerous human diseases are associated with mutations and mislocalization of NETs on the NE. There are still many fundamental questions that are unresolved with NETs, but we focused on two major questions: First, the localization and transport rate of NETs, and second, the transport route taken by NETs to reach the INM. Since NETs are involved with many of the mechanisms used to maintain cellular homeostasis, it is important to quantitatively determine the spatial locations of NETs along the NE to fully understand their role in these vital processes. However, there are limited available approaches for this task, and moreover, these methods provide no information about the translocation rates of NETs between the two membranes. Furthermore, while the trafficking of soluble proteins between the cytoplasm and the nucleus has been well studied over the years, the path taken by NETs into the nucleus remains in dispute. At least four distinct models have been proposed to suggest how transmembrane proteins destined for the INM cross the NE through NPC-dependent or NPC-independent mechanisms, based on specific features found on the soluble domains of INM proteins. In order to resolve these two major questions, it is necessary to employ techniques with the capabilities to observe these dynamics at the nanoscale. Current experimental techniques are unable to break the temporal and spatial resolution barriers required to study these phenomena. Therefore, we developed and modified single-molecule techniques to answer these questions. First, to study the distribution of NETs on the NE, we developed a new single-molecule microscopy method called single-point single-molecule fluorescence recovery after photobleaching (smFRAP), which is able to provide spatial resolution <10 nm and, furthermore, provide previously unattainable information about NET translocation rates from the ONM to INM. Secondly, to examine the transport route used by NETs destined for the INM, we used a single-molecule microscopy technique previously developed in our lab called single-point edge-excitation sub-diffraction (SPEED) microscopy, which provides spatio-temporal resolution of <10 nm precision and 0.4 ms detection time. The major findings from my doctoral research work can be classified into two categories: (i) Technical developments to study NETs in vivo, and (ii) biological findings from employing these microscopy techniques. In regards to technical contributions, we created and validated of a new single-molecule microscopy method, smFRAP, to accurately determine the localization and distribution ratios of NETs on both the ONM and INM in live cells. Second, we adapted SPEED microscopy to study transmembrane protein translocation in vivo. My work has also contributed four main biological findings to the field: first, we determined the in vivo translocation rates for lamin-B receptor (LBR), a major INM protein found in the nucleus of cells. Second, we verified the existence of peripheral channels in the scaffolding of NPCs and, for the first time, directly observed the transit of INM proteins through these channels in live cells. Third, our research has elucidated the roles that both the nuclear localization signal (NLS) and intrinsically disordered (ID) domains play in INM protein transport. Finally, my work has elucidated which transport routes are used by NETs destined to localize in the INM.
Temple University--Theses
Alvarado, Walter. "Investigating Butyrylcholinesterase Inhibition via Molecular Mechanics." Thesis, California State University, Long Beach, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10639439.
Повний текст джерелаWe show that a combination of different theoretical methods is a viable approach to calculate and explain the relative binding affinities of inhibitors of the human butyrylcholinesterase enzyme. We probe structural properties of the enzyme-inhibitor complex in the presence of dialkyl phenyl phosphates and derivatives that include changes to the aromatic group and alkane-to-cholinyl substitutions that help these inhibitors mimic physiological substrates. Monte Carlo docking allowed for the identification of three regions within the active site of the enzyme where substituents of the phosphate group could be structurally stabilized. Computational clustering was used to identify distinct binding modes and their relative stabilities. Molecular dynamics suggest an essential asparagine residue not previously characterized as strongly influencing inhibitor strength which may serve as a crucial component in catalytic and inhibitory activity. This study provides a framework for suggesting future inhibitors that we expect will be effective at sub-micromolar concentrations.
Good, Benjamin Harmar. "Molecular Evolution in Rapidly Evolving Populations." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493449.
Повний текст джерелаPhysics
Kind, Peter. "Molecular studies of development and plasticity in the visual system." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333399.
Повний текст джерелаChadborn, Neil H. "Molecular properties of albumin underlie its role in cellular physiology." Thesis, University of Essex, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310053.
Повний текст джерелаMiller, Helen. "Novel super-resolution optical microscopy methods for single-molecule biophysics." Thesis, University of York, 2017. http://etheses.whiterose.ac.uk/18192/.
Повний текст джерелаRisal, Laxmi. "STUDY OF PRESSURE DEPENDENCE OF MOLECULAR CONFORMATION OF NADH USING SPECTRAL PHASOR ANALYSIS." Miami University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=miami1469015215.
Повний текст джерелаHuseby, Carol. "Molecular Neuropathology in Alzheimer's Disease." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1543314678552794.
Повний текст джерелаFord, Jaqueline. "Biophysical and molecular studies on peripheral retinal proteins." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335776.
Повний текст джерелаHartman, Adam Z. "Effects of nanoconfinement on molecular motors : collective kinesin behavior, external modulation, and applications to molecular transport." View abstract/electronic edition; access limited to Brown University users, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3318324.
Повний текст джерелаLi, Tong. "Cross-scale biophysics modelling of F-actin cytoskeleton in cell." Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/82293/1/Tong_Li_Thesis.pdf.
Повний текст джерелаYousef, Diana O. "Structural and functional characterization of the lumenal portion of putative cargo receptor, yp24A/Emp24p /." Access full-text from WCMC:, 2007. http://proquest.umi.com/pqdweb?did=1296098021&sid=3&Fmt=2&clientId=8424&RQT=309&VName=PQD.
Повний текст джерелаLEE, SEONG-KI. "Molecular Action of an Electrogenic Na/HCO3 Cotransporter (NBCe1)." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1373037484.
Повний текст джерелаWollman, Adam J. M. "DNA motor-protein hybrids for molecular transport and self-organisation." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:907144ad-2eec-4c01-8f20-217a1b7c122c.
Повний текст джерелаHigham, Richard G. "A biophysical analysis of the Ocr protein gel." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/2569.
Повний текст джерелаAl-Yatama, Fatima Ibrahim Khalaf. "Maternal hypothyroxinemia and fetal brain development : biochemical, enzymic, metabolic and molecular biological investigation." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362383.
Повний текст джерелаLim, Ren Chong. "Application of magnetic torque on the bacterial flagellar motor." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:2f18fdff-e876-4be6-8ac2-c8281a4a905a.
Повний текст джерелаNauseef, Jones Trevor. "An investigation of the molecular and biophysical properties of metastatic cells." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/3150.
Повний текст джерелаCosta, Laiana Cristina da [UNESP]. "Estudos dos efeitos de carga e da hidrofobicidade na interação de peptídeos antimicrobianos e membranas modelo." Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/87519.
Повний текст джерелаCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Mastoparanos são uma família de peptídeos líticos, extraídos do saco de veneno de vespas sociais, que apresentam moderada a intensa atividade antimicrobiana e alguns são hemolíticos e citotóxicos. Embora o mecanismo de ação destes peptídeos não seja bem compreendido ainda, aceita-se que envolva desestabilização da fase lipídica da membrana celular. Acredita-se que a carga líquida do peptídeo e sua hidrofobicidade média contribuam na modulação da atividade lítica e na seletividade. Nesta dissertação apresentamos um estudo de quatro peptídeos mastoparanos que possuem resíduos ácidos e básicos resultando em uma carga elétrica líquida variando de +1 a +4. Este estudo envolve a análise conformacional destes peptídeos em vesículas zwitteriônicas e aniônicas por dicroísmo circular. Suas atividades líticas foram avaliadas usando espectroscopia de fluorescência monitorando a recuperação da intensidade de fluorescência devido à liberação de marcador fluorescente encapsulado em vesículas. As constantes de partição destes peptídeos em vesículas zwitteriônicas foram também determinadas por espectroscopia de fluorescência usando um método de análise que é independente de modelo. Com o objetivo de entender a influência de resíduos ácidos e a carga líquida dos peptídeos e sua hidrofobicidade na interação peptídeo-lipídio, foram estimadas as contribuições energéticas eletrostáticas e não eletrostática. Para alcançar este objetivo, os resultados obtidos nas isotermas de ligação por fluorescência foram associados com medidas de potencial zeta. Foi observado que a afinidade destes peptídeos em vesículas zwitteriônicas decresce com a carga líquida do peptídeo e as curvas de dose-resposta são mais cooperativas para os dois peptídeos com as cargas mais baixas. Os peptídeos com maior carga apresentaram uma maior afinidade...
Mastoparans are a family of lytic peptides extracted from the venom sac of wasps which present moderate to intense antimicrobial activity and some of them are hemolytic and cytotoxic. Although the mechanism of action of these peptides are still not completely understood, it is accepted that it involves the destabilization of the lipidic phase of the cell membrane. It is believed that both the peptide net electrical charge and its mean hydrophobicity contribute to modulate their lytic activity and selectivity. In this dissertation we present a study of four mastoparan peptides which have acidic and basic residues resulting in net electrical charges ranging from +1 to +4. This study involves the conformational analysis of these peptides in zwitterionic and anionic lipid vesicles by circular dichroism. Their lytic activities were evaluated using fluorescence spectroscopy by the release of fluorescent dye entrapped in these two types of vesicles. The partition constants of these peptides to zwitterionic vesicles were also determined by fluorescence spectroscopy using a method of analysis which is model independent. Aiming to understand the influence of acidic residues and of the peptides net charge and hydrophobocity on the peptide-lipid interaction, the electrostatic and non electrostatic energetic contributions were estimated. To achieve this goal it was used the association of the results of fluorescence binding isotherms and zeta potential measurements. It was observed that the affinity and lytic activity of these peptides in zwitterionic vesicles decrease with the peptides net electrical charges and the dose-response curves are more cooperative for the two peptides with lower net charges. The more charged peptides exhibit higher affinity and lytic activity in anionic vesicles. The most charged peptide displayed the higher selectivity for the vesicles studied. The present work... (Complete abstract click electronic access below)