Gotowe bibliografie tematyczne / Moleculor Biophysics / Rozprawy doktorskie
Kliknij ten link, aby zobaczyć inne rodzaje publikacji na ten temat: Moleculor Biophysics.

Rozprawy doktorskie na temat „Moleculor Biophysics”

Autor: Grafiati
Data publikacji: 6 września 2023

Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych

Wybierz rodzaj źródła:

Sprawdź 50 najlepszych rozpraw doktorskich naukowych na temat „Moleculor Biophysics”.

Przycisk „Dodaj do bibliografii” jest dostępny obok każdej pracy w bibliografii. Użyj go – a my automatycznie utworzymy odniesienie bibliograficzne do wybranej pracy w stylu cytowania, którego potrzebujesz: APA, MLA, Harvard, Chicago, Vancouver itp.

Możesz również pobrać pełny tekst publikacji naukowej w formacie „.pdf” i przeczytać adnotację do pracy online, jeśli odpowiednie parametry są dostępne w metadanych.

Przeglądaj rozprawy doktorskie z różnych dziedzin i twórz odpowiednie bibliografie.

1

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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
2

Teng, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
3

Elmlund, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
4

Neetz, 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.

Pełny tekst źródła
Streszczenie:
Microtubule associated molecular motors are involved in a multitude of fundamental cellular processes such as intracellular transport and spindle positioning. During these movements multiple motor proteins often work together and are, therefore, able to exert high forces. Thus force generation and sensing are common mechanisms for controlling motor driven movement. These mechanisms play a pivotal role when motor proteins antagonize each other, e.g. to facilitate oscillations of the spindle or the nucleus. Single motor proteins have been characterized in depth over the last two decades, our understanding of the collective behavior of molecular motors remains, however, poor. Since motor proteins often cooperate while they walk along microtubules, it is necessary to describe their collective reaction to a load quantitatively in order to understand the mechanism of many motor-driven processes. I studied the antagonistic action of many molecular motors (of one kind) in a gliding geometry. For this purpose I crosslinked two microtubules in an antiparallel fashion, so that they formed \"doublets\". Then I observed the gliding motility of these antiparallel doublets and analyzed the gliding velocity with respect to the relative number of motors pulling or pushing against each other. I observed that the antiparallel doublets gliding on conventional kinesin-1 (from Drosophila melanogaster) as well as cytoplasmic dynein (from Saccharomyces cerevisae) exhibited two distinct modes of movement, slow and fast, which were well separated. Furthermore I found a bistability, meaning, that both kinds of movement, slow and fast, occurred at the same ratio of antagonizing motors. Antiparallel doublets gliding on the non-processive motor protein Ncd (the kinesin-14 from D. melanogaster) showed, however, no bistability. The collective dynamics of all three motor proteins were described with a quantitative theory based on single-motor properties. Furthermore the response of multiple dynein motors towards an external, well-defined load was measured in a gliding geometry by magnetic tweezing. Examples of multi-motor force-velocity relationships are presented and discussed. I established, furthermore, a method for counting single surface immobilized motors to guide the evaluation of the tweezing experiments.
Style APA, Harvard, Vancouver, ISO itp.
5

Shen, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
6

Mukund, Shreyas Ram. "Single molecule biophysics of homologous recombination". Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708842.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
7

Tang, 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.

Pełny tekst źródła
Streszczenie:
This thesis explores the biophysics of collagen in the extracellular matrix under external stimuli, by performing cutting edge MD simulations. The obtained results provide significant insights into the design and manufacturing of artificial biomaterials for surgical tissue treatments, of collagen for regenerative medicine applications, and of gold nanoparticles for biomedical applications. The probed biophysical properties consist of the structural properties and the mechanical properties, where the mechanical properties of collagen are regulated by its structure at different levels of hierarchies.
Style APA, Harvard, Vancouver, ISO itp.
8

Klingelhoefer, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
9

Bellaiche, 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.

Pełny tekst źródła
Streszczenie:
In this thesis, we investigate the mechanisms driving the self-assembly of peptides and proteins using computational and theoretical tools, always validating our results with experimental measures when possible. In the first part, Chapters 2-5, we focus on the Aβ system, a peptide whose aggregation is intimately linked with the development of Alzheimer's Disease. We begin by simulating the major alloforms of the peptide, Aβ_40 and Aβ_42, demonstrating that the two populate similar disordered ensembles and matching experimental data. Next we investigate how disordered Aβ_42 monomers interact with each other, finding that oligomerisation into amorphous aggregates is driven largely by hydrophobic, non-specific forces. We then move on to probing the aggregation of Aβ_42 into amyloid structures using a native-centric coarse-grained model, and explain the results with a novel Markov state analysis from which we are able to extract structural, kinetic and thermodynamic information on elongation reactions. Finally, we probe the interactions of Aβ_42 monomers with Aβ_42 fibrillar surfaces using a specially designed enhanced sampling scheme, which allows us to obtain enthalpy-driven binding thermodynamics consistent with experiments and to propose major polar binding modes. In the second part of the thesis, Chapters 6 and 7, we model the aggregation of two other self-assembling systems, viruses and a truncated form of the molecular chaperone Hsp70. We first develop a data analysis platform to extract information on the microscopic mechanisms of viral capsid self-assembly from experimental data, synthesising the results from several different systems to draw general evolutionary conclusions about the assembly mechanism. Finally, we model the oligomerisation of Hsp70 thermodynamically and kinetically, showing that its self-assembly is a highly cooperative reaction that is under strong structural constraints.
Style APA, Harvard, Vancouver, ISO itp.
10

King, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
11

Bondar, Ana-Nicoleta [Verfasser]. "Computational Molecular Biophysics of Membrane Reactions / Ana-Nicoleta Bondar". Berlin : Freie Universität Berlin, 2020. http://d-nb.info/121464144X/34.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
12

Koga, Daniel Inoue [UNESP]. "Análise vibracional do α-tocoferol". Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/87501.

Pełny tekst źródła
Streszczenie:
Made available in DSpace on 2014-06-11T19:22:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-29Bitstream added on 2014-06-13T20:10:03Z : No. of bitstreams: 1 koga_di_me_sjrp.pdf: 1553861 bytes, checksum: f88c5801e8c2256d97ed7327d979e856 (MD5)
Conselho 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.
Style APA, Harvard, Vancouver, ISO itp.
13

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.

Pełny tekst źródła
Streszczenie:
Molecular biophysics is a rapidly evolving field aimed at the physics-based investigation of the biomolecular processes that enable life. In this thesis, we explore two such processes: the thermodynamics of DNA bending, and the mechanism of the RecQ DNA helicase. A computational approach using a coarse-grained model of DNA is employed for the former; an experimental approach relying heavily on single-molecule fluorescence for the latter. There is much interest in understanding the physics of DNA bending, due to both its biological role in genome regulation and its relevance to nanotechnology. Small DNA bending fluctuations are well described by existing models; however, there is less consensus on what happens at larger bending fluctuations. A coarse-grained simulation is used to fully characterize the thermodynamics and mechanics of duplex DNA bending. We then use this newfound insight to harmonize experimental results between four distinct experimental systems: a 'molecular vise', DNA cyclization, DNA minicircles and a 'strained duplex'. We find that a specific structural defect present at large bending fluctuations, a 'kink', is responsible for the deviation from existing theory at lengths below about 80 base pairs. The RecQ DNA helicase is also of much biological and clinical interest, owing to its essential role in genome integrity via replication, recombination and repair. In humans, heritable defects in the RecQ helicases manifest clinically as premature aging and a greatly elevated cancer risk, in disorders such as Werner and Bloom syndromes. Unfortunately, the mechanism by which the RecQ helicase processes DNA remains poorly understood. Although several models have been proposed to describe the mechanics of helicases based on biochemical and structural data, ensemble experiments have been unable to address some of the more nuanced questions of helicase function. We prepare novel substrates to probe the mechanism of the RecQ helicase via single-molecule fluorescence, exploring DNA binding, translocation and unwinding. Using this insight, we propose a model for RecQ helicase activity.
Style APA, Harvard, Vancouver, ISO itp.
14

Elnatan, Daniel. "Asymmetric Mechanism of Molecular Chaperone Hsp90". Thesis, University of California, San Francisco, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10690095.

Pełny tekst źródła
Streszczenie:

Hsp90 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.

Style APA, Harvard, Vancouver, ISO itp.
15

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.

Pełny tekst źródła
Streszczenie:
This thesis is focused on the study of molecular interactions at the atomistic detail and is divided into one introductory chapter and four chapters referencing different problems and methodological approaches. All of them are focused on the development and improvement of computational Monte Carlo algorithms to study, in an efficient manner, the behavior of these systems at a classical molecular mechanics level. The four biophysical problems studied in this thesis are: induced fit docking between protein-ligand and between DNA-ligand to understand the binding mechanism, protein stretching response, and generation/ scoring of protein-protein docking poses. The thesis is organized as follows: First chapter corresponds to the state of the art in computational methods to study biophysical interactions, which is the starting point of this thesis. Our in-house PELE algorithm and the main standard methods such as molecular dynamics will be explained in detail. Chapter two is focused on the main PELE modifications to add new features, such as the addition of a new force field, implicit solvent and an anisotropic network specific for DNA simulation studies. We study, compare and validate the conformations generated by six representative DNA fragments with the new PELE features using molecular dynamics as a reference. Chapter three is devoted to applying the new methods implemented and tested in PELE to study protein-ligand interactions and DNA-ligand interactions using four systems. First, we study the porphyrin binding to Gun4 protein combining PELE and molecular dynamics simulations. Besides, we provide a docking pose that has been corroborated by a new crystal structure published during the revision process of the submitted study showing the accuracy of our predictions. In the second project, we use our improved version of PELE to generate the first structural model of an alpha glucose 1,6-bisphosphate substrate bound to the human Phosphomannomutase 2 demonstrating that this ligand can adopt two low-energy orientations. The third project is the study of DNA-ligand interactions for three cisplatin drugs where we evaluate the binding free energy using Markov state models. We show excellent results respect another free energy methods studied with molecular dynamics. The last project is the study of the daunomycin DNA intercalator where we simulate and study the binding process with PELE. Chapter four is focused on the computational study of force extension profiles during the protein unfolding. We added a dynamic harmonic constraint following a similar procedure applied in steered molecular dynamics to our Monte Carlo approach to fix or pull some selected atoms forcing the protein unfolding in a defined direction. We implement and compare with steered molecular dynamics this technique with Ubiquitin and Azurin proteins. Moreover, we add this feature to a well-known algorithm called MCPRO from William Jorgensen¿s group at YALE University to evaluate the free energy associated to the unfolding of the deca-alanine system. Chapter five corresponds to the introduction of a multiscale approach to study protein-protein docking. A coarse-grained model will be combined with a Monte Carlo exploration reducing the degrees of freedom to generate thousands of protein-protein poses in a quick way. Poses produced by this procedure will be refined and ranked through a protonation, hydrogen bond optimization, and minimization protocol at the all-atom representation to identify the best poses. I present two test cases where this procedure has been applied showing a good accuracy in the predictions: tryptogalinin and ferredoxin/flavodoxin systems.
Aquesta 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.
Style APA, Harvard, Vancouver, ISO itp.
16

Le, Tung T. "Single-molecule biophysics of DNA bending: looping and unlooping". Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/53979.

Pełny tekst źródła
Streszczenie:
DNA bending plays a vital role in numerous cellular activities such as transcription, viral packaging, and nucleosome formation. Therefore, understanding the physics of DNA bending at the length scales relevant to these processes is one of the main keys to the quantitative description of life. However, previous studies provide a divided picture on how DNA should be modeled in strong bending condition relevant to biology. My thesis is devoted to answering how far an elastic rod model can be applied to DNA. We consider several subtle features that could potentially lead to the break-down of the worm-like chain model, such as local bendedness of the sequence and large bending angles. We used single-molecule Fluorescence Resonance Energy Transfer to track looping and unlooping of single DNA molecules in real time. We compared the measured looping and unlooping rates with theoretical predictions of the worm-like chain model. We found that the intrinsic curvature of the sequence affects the looping propensity of short DNA and an extended worm-like chain model including the helical parameters of individual base pairs could adequately explain our measurements. For DNA with random sequence and negligible curvature, we discovered that the worm-like chain model could explain the stability of small DNA loops only down to a critical loop size. Below the critical loop size, the bending stress stored in the DNA loop became less sensitive to loop size, indicative of softened dsDNA. The critical loop size is sensitive to salt condition, especially to magnesium at mM concentrations. This finding enabled us to explain several contrasting results in the past and shed new light on the energetics of DNA bending.
Style APA, Harvard, Vancouver, ISO itp.
17

Koussa, Mounir Ahmad. "The Biophysics of Vertebrate Hearing: A Single-Molecule Approach". Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467499.

Pełny tekst źródła
Streszczenie:
Inner-ear mechanotransduction relies on tip links, fine protein filaments made of cadherin-23 and protocadherin-15 that convey tension to mechanosensitive channels at the tips of hair-cell stereocilia. The tip-link cadherins are thought to form a heterotetrameric complex, with two cadherin-23 molecules forming the upper part of the filament and two protocadherin-15 molecules forming the lower end. The interaction between cadherin-23 and protocadherin-15 is mediated by their N-terminal tips. Missense mutations that modify the interaction interface impair binding and lead to deafness. We have developed molecular tools to perform single-molecule force spectroscopy on the tip-link bond. Self-assembling DNA nanoswitches are functionalized with the interacting tips of cadherin-23 and protocadherin-15 using the enzyme sortase under conditions that preserve protein function. These tip-link-functionalized nanoswitches are designed to provide a signature force-extension profile, which allows us to identify single-molecule rupture events that result from applying force. Using this system, we have been able to measure the cadherin-23-protocadherin-15 single-molecule force-dependent off rate, as well as the concentration-dependent on rate for a single pair of these proteins. The rates suggest that a single bond is inadequate to withstand physiological forces for physiological times, but we construct a new model for tip-link dynamics which greatly alters our understanding of tip-link function and explains the necessity for a two-filament tip link.
Medical Sciences
Style APA, Harvard, Vancouver, ISO itp.
18

Tesdahl, Natalya S. "Molecular basis of autism-like behavior in SAPAP3-deficient mice". Thesis, University of Iowa, 2017. https://ir.uiowa.edu/etd/5657.

Pełny tekst źródła
Streszczenie:
Autism Spectrum Disorders (ASDs) are a diverse group of diseases that share the common features of deficits in social communication and rigid, repetitive behavior patterns. Most genetic alterations related to ASD can be broadly split into two categories – those pertaining to mTOR/PI3K signaling, and those pertaining to synaptic connections and structure. While a number of synaptic scaffolding proteins have been linked to ASD via human genetic studies and mouse models, SAP90/PSD95 associated protein 3 (SAPAP3) has not. Loss of SAPAP3 in mice, however, results in compulsive grooming behavior, which parallels one of the core features of ASD. On a molecular level, loss of SAPAP3 results in increased signaling via the group I metabotropic glutamate receptor mGluR5. As mGluR5 is known to regulate protein transcription and translation, we conducted a proteomic comparison of sapap3-/- mice relative to sapap3+/+ mice. We identified a number of differentially regulated proteins, the majority of which were upregulated in sapap3-/- mice. Of those, we chose to further investigate collapsin response mediator protein 2 (CRMP2), due to its role in regulating dendritic branching and neurogenesis. We found abnormalities in both dendritic branching and postnatal neurogenesis in sapap3-/- mice, changes which may contribute to some of their behavioral phenotypes. We also found that ultrasonic vocalization, a form of communication for mice, is altered in neonatal sapap3-/- mice. Taken together, these findings provide new direction that could lead to future therapeutics for patients with ASD, as well as an early read-out of the effectiveness of any potential treatment.
Style APA, Harvard, Vancouver, ISO itp.
19

Goryaynov, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
20

Jones, Nathan Jones. "Single Molecule Analysis of DNA Interactions". The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1511959163350735.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
21

Adcock, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
22

Roman, 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.

Pełny tekst źródła
Streszczenie:
The latch-state is the capacity of smooth muscle to maintain force for long periods of time with low energy consumption. The prevalent theory to explain the latch-state suggests that if myosin gets deactivated (dephosphorylated) while attached to actin, it remains attached and maintains force. Other theories suggest that dephosphorylated and detached myosin can bind to actin to maintain force and that actin regulatory proteins participate in the force maintenance. All theories of the latch-state were based on measurements performed at the whole muscle level and were never confirmed at the molecular level. Verifying the latch-state theories at the molecular level was the main goal of this thesis.To further our understanding of the latch-state, the role of calponin in the binding of unphosphorylated myosin to actin was determined. The laser trap assay was used to measure the average force of unbinding (Funb) in the absence and presence of calponin. Calponin enhanced the Funb. Phosphorylation of calponin with Ca2+-calmodulin dependant protein kinase II, which detaches calponin from actin, decreased the Funb to the unregulated actin level. Performing the measurements at high ionic strength, which detaches calponin from myosin, had the same effect on the Funb. These later two measurements demonstrate that calponin enhances the Funb of unphosphorylated myosin to actin by crosslinking them together. Next, the effect of caldesmon on the Funb was studied; caldesmon enhanced the Funb. Because tropomyosin is known to potentiate biochemical and mechanical effects of caldesmon, its action on the Funb in combination with caldesmon was also measured. Tropomyosin enhanced the Funb on its own but had no synergistic effect with caldesmon. Phosphorylation of caldesmon with the extracellular signal-regulated kinase (ERK) decreased the Funb below the unregulated actin level. Because ERK phosphorylation of caldesmon occurs late in the contraction, this last result suggests a relaxation mechanism from the latch-state. Examination of the force traces revealed a visco-elastic behavior of myosin in the presence of ERK phosphorylated caldesmon which either prevents binding or promotes detachment from actin, thus leading to muscle relaxation. Finally, the ultimate molecular level demonstration of the latch-state requires dephosphorylation of myosin during molecular force measurements with a laser trap assay. However, addition of myosin light chain phosphatase cannot be done without disturbing the single molecule level mechanics measurements. Thus, a microfluidic device was designed and developed to allow the addition of chemicals to a molecular mechanics flow-through chamber without creating any bulk flow. A micro-channel chamber was created by standard photolithography on silicon wafers with the patterns transferred to polymethylsiloxane (PDMS). The chamber was then bound to a polycarbonate membrane which itself was bound to the molecular mechanics chamber. The micro-channels assured rapid distribution of the chemicals whereas the membrane assured efficient delivery but prevented bulk flow. The device was tested by injection of adenosine triphosphate to initiate the propulsion of actin by myosin. The proof of principle of this microfluidic device concludes this thesis.
Le 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.
Style APA, Harvard, Vancouver, ISO itp.
23

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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
24

Marshall, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
25

Hanlon, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
26

Sloutsky, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
27

Ishimaru, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
28

Crawford, 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.

Pełny tekst źródła
Streszczenie:
Gene regulation is vital to the success of all living organisms. Understanding this complex process is crucial to our knowledge of how cells function and how in some cases they can lead to debilitating or even fatal disease. In this thesis I focus on a set of DNA-binding proteins known as transcription factors (TFs), proteins fundamental to the process of gene regulation at the level of transcription. I develop assays and techniques for the detection and quantitation of TFs in vitro and in vivo as well as a method for TF encapsulation and release. The advantages of the TF detection assays in this thesis are made possible through the use of single-molecule (sm) fluorescence. This methodology enables detection of individually labeled molecules allowing discrimination of sample heterogeneities inaccessible with ensemble techniques. Here I present two different TF assays based on two sm observables: relative probe stoichiometry and Förster resonance energy transfer (FRET). The first assay design, based on stoichiometry, detects TFs using TF-dependent coincidence of two distinctly labelled DNA ‘half-sites’. I demonstrate sensitive detection (~ pM) in solution and on surfaces, multiplexed detection of multiple TFs, and detection in cell lysates. A kinetic model of the system is also developed, verified experimentally and used to quantify TF concentrations without the need for a calibration curve. The second assay design, based on FRET, is a novel approach to TF detection using TFmediated DNA bending. TFs are detected by bending the sensor and monitored with FRET at the single-molecule or ensemble level. I demonstrate TF detection in purifed form and expressed in cell lysates. As this sensor was designed for use in vivo, methods to hinder nuclease degradation are explored. For TF detection in vivo, I describe a successful strategy to internalise fluorescently labeled molecules into live E.coli. Viability and internalisation efficiency are characterised and ensemble measurements with FRET standards are demonstrated. Importantly, sm FRET measurements in vivo are achieved opening many exciting possibilities. The FRET based TF sensor is then internalised as a step towards real-time in vivo monitoring of TF concentrations. Finally a system based on DNA nanotechnology is presented for the non-covalent encapsulation and release of TFs. Such a system could be delivered into a cell to alter levels of gene expression using external stimuli as inputs. We believe these tools will generate valuable information in the study of prokaryotic gene expression as well as providing a potential commercial avenue towards diagnostics.
Style APA, Harvard, Vancouver, ISO itp.
29

Koga, Daniel Inoue. "Análise vibracional do α-tocoferol /". São José do Rio Preto : [s.n.], 2010. http://hdl.handle.net/11449/87501.

Pełny tekst źródła
Streszczenie:
Orientador: Marinônio Lopes Cornélio
Banca: 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
Style APA, Harvard, Vancouver, ISO itp.
30

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.

Pełny tekst źródła
Streszczenie:
Macromolecular transitions such as conformational changes and protein-protein association underlie many biological processes. Conformational changes in the N-terminal domain of the transmembrane protein DsbD (nDsbD) were studied by NMR and molecular dynamics (MD) simulations. nDsbD supplies reductant to biosynthetic pathways in the oxidising periplasm of Gram-negative bacteria after receiving reductant from the C-terminal domain of DsbD (cDsbD). Reductant transfer in the DsbD pathway happens via protein-protein association and subsequent thiol-disulphide exchange reactions. The cap loop shields the active-site cysteines in nDsbD from non-cognate oxidation, but needs to open when nDsbD bind its interaction partners. The loop was rigid in MD simulations of reduced nDsbD. More complicated dynamics were observed for oxidised nDsbD, as the disulphide bond introduces frustration which led to loop opening in some trajectories. The simulations of oxidised and reduced nDsbD agreed well with previous NMR spin-relaxation and residual dipolar coupling measurements as well as chemical shift-based torsion angle predictions. NMR relaxation dispersion experiments revealed that the cap loop of oxidised nDsbD exchanges between a major and a minor conformation. The differences in their conformational dynamics may explain why oxidised nDsbD binds its physiological partner cDsbD much tighter than reduced nDsbD. The redox-state dependent interaction between cDsbD and nDsbD is thought to enhance turnover. NMR relaxation dispersion experiments gave insight into the kinetics of the redox-state dependent interaction. MD simulations identified dynamic encounter complexes in the association of nDsbD with cDsbD. The mechanism of the conformational changes in the transport cycle of LacY were also investigated. LacY switches between periplasmic open and cytoplasmic open conformations to transport sugars across the cell membrane. Two mechanisms have been proposed for the conformational change, a rocker-switch mechanism based on rigid body motions and an “airlock” like mechanism in which the transporter would switch conformation via a fully occluded structure. In MD simulations using the novel dynamics importance sampling approach such a fully occluded structure was found. The simulations argued against a strict “rocker-switch” mechanism.
Style APA, Harvard, Vancouver, ISO itp.
31

Samanta, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
32

Mudumbi, 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.

Pełny tekst źródła
Streszczenie:
Biology
Ph.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
Style APA, Harvard, Vancouver, ISO itp.
33

Alvarado, Walter. "Investigating Butyrylcholinesterase Inhibition via Molecular Mechanics". Thesis, California State University, Long Beach, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10639439.

Pełny tekst źródła
Streszczenie:

We 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.

Style APA, Harvard, Vancouver, ISO itp.
34

Good, Benjamin Harmar. "Molecular Evolution in Rapidly Evolving Populations". Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493449.

Pełny tekst źródła
Streszczenie:
Advances in DNA sequencing are creating new opportunities for studying the process of evolution. These measurements can be particularly useful for rapidly evolving microbial organisms, whose small size and fast generation times make them ideal for controlled laboratory experiments and for tracking replicate populations in vivo. However, the interpretation of this new source of data is complicated by the unique ways in which these large microbial populations evolve. The basic problem is that natural selection is forced to do too many things at once. Unlike the classical picture, where new mutations arise one-by-one, rapidly evolving populations often harbor many selected variants at the same time. When recombination is limited, selection cannot act on these mutations individually, but only on combinations of mutations that happen to arise on the same genetic background. These effects, known as clonal interference, create correlations along the genome that are difficult to disentangle. Existing population genetic models often neglect these effects, which leaves us at loss when interpreting data from these populations. In Chapters 2-5, we analyze the effects of clonal interference in a simple ``null model'' of microbial evolution. We focus on the simplest model that is consistent with two empirical observations: (1) many fitness-influencing mutations are created every generation and (2) mutations have a broad range of fitness effects. After analyzing the basic dynamics of this model, we obtain predictions for the substitution rates of individual mutations and the patterns of linked neutral diversity, and we show how these quantities depend on the population size, mutation and recombination rates, and the fitness effects of new mutations. In Chapters 6 and 7, we apply this null model to data from laboratory experiments in S. cerevisiae and E. coli. We develop a statistical framework to infer the underlying parameters (the fitness effects of new mutations), which allows us to quantify deviations from the model over longer evolutionary timescales. Finally, in Chapters 8 and 9, we investigate the behavior of the model when some of the parameters are allowed to evolve or change in time.
Physics
Style APA, Harvard, Vancouver, ISO itp.
35

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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
36

Chadborn, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
37

Miller, Helen. "Novel super-resolution optical microscopy methods for single-molecule biophysics". Thesis, University of York, 2017. http://etheses.whiterose.ac.uk/18192/.

Pełny tekst źródła
Streszczenie:
Super-resolution microscopy is a relatively new and rapidly growing field. Development has been largely technology-driven, with high power lasers, higher resolution CCD cameras, and increasing computing power all enabling new biological questions to be explored. Single-molecule imaging is the tool of choice for studying systems where heterogeneity is present; ensemble methods can average away the interesting behaviour and lead to false conclusions. This thesis develops and optimises bespoke fluorescence microscopy for application to three biological questions, each pushing a limit of super-resolution imaging. Super-resolution imaging of lambda DNA labelled with the intercalating dye YOYO-1 and the minor groove binder SYTO-13 at localisation precisions of 40nm and 62nm respectively has been achieved in preparation for combined fluorescence imaging and magneto-optical tweezers experiments. The combination of these two methods is challenging as both operate with low tolerances.\ Single-molecule tracking was used to measure the diffusion coefficients of the chemokines CXCL13 and CCL19 at extremely high temporal resolution. Single-molecule imaging was found to have advantages over the ensemble techniques of FRAP and FCS for measuring the diffusion coefficient of the test molecule; Alexa Fluor 647 labelled bovine serum albumin. The diffusion coefficients of the two chemokines, CXCL13 and CCL19 were found by single particle tracking at sub-millisecond timescales in a collagen matrix to be 6.2±0.3µm2s-1 and 8.4±0.2µm2s-1. Further, CXCL13 was tracked in B cell follicle regions of ex vivo lymph node tissue sections at ~2 millisecond timescales, giving a diffusion coefficient of 6.6±0.4µm2s-1.\ Fluorescence microscopy was used to elucidate the stoichiometry of YOYO-1 on DNA origami tiles after treatment with low temperature plasma. Undamaged tiles were found to have a mean stoichiometry of 67.4±25.2 YOYO-1 molecules and a model of LTP damage to DNA origami tiles was proposed.
Style APA, Harvard, Vancouver, ISO itp.
38

Risal, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
39

Huseby, Carol. "Molecular Neuropathology in Alzheimer's Disease". The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1543314678552794.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
40

Ford, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
41

Hartman, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
42

Li, 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.

Pełny tekst źródła
Streszczenie:
This thesis is a comparative study of the modelling of mechanical behaviours of F-actin cytoskeleton which is an important structural component in living cells. A new granular model was developed for F-actin cytoskeleton based on the concept of multiscale modelling. This framework overcomes difficulties encountered in physical modelling of cytoskeleton in conventional continuum mechanics modelling, and the computational challenges in all-atom molecular dynamics simulation. The thermostat algorithm was further modified to better predict the thermodynamic properties of F-actin cytoskeleton in modelling. This multiscale modelling framework was applied in explaining the physical mechanisms of cytoskeleton responses to external mechanical loads.
Style APA, Harvard, Vancouver, ISO itp.
43

Yousef, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
44

LEE, 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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
45

Wollman, 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.

Pełny tekst źródła
Streszczenie:
Kinesin is a molecular motor which walks on microtubule tracks in the eukaryotic cytoskeleton. It transports cargo but is also involved in cytoskeletal organisation. This thesis demonstrates fusing kinesin and DNA to construct a molecular transport system using self-organised tracks and to study the mechanics of the minimal motor unit of kinesin. The programmability of DNA allows for the formation of nanostructures with controllable interactions. Kinesin is conjugated to various DNA nanostructures to accomplish different tasks. Instructions encoded into DNA sequences are used to direct the assembly of a polar array of microtubules, to control the loading, active concentration and unloading of cargo on this track network and to trigger the disassembly of the network. Fluorescence microscopy was used to observe these microtubule arrays and the movement of cargo. It was found that the DNA signals used to control the unloading of cargo and the disassembly of the network had to be actively transported, rather than relying on diffusion, for effective delivery of the signal. This work lead to a first author publication, Wollman et al. (2013). DNA was also used to study kinesin by linking defined numbers of minimal functional motor units, single kinesin heads, into teams of 4-12 heads and observing their movement along microtubules via fluorescent labelling. A minimum of 5 heads were required for sustained movement, in agreement with the predictions of Hancock and Howard (1998). The velocity of teams increased with more heads, up to 8, and then a decrease was observed in teams with more heads.
Style APA, Harvard, Vancouver, ISO itp.
46

Higham, Richard G. "A biophysical analysis of the Ocr protein gel". Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/2569.

Pełny tekst źródła
Streszczenie:
Ocr is unusual among proteins in its ability to form a transparent gel at high ammonium sulphate concentrations. This transition was investigated using a combination of spectroscopic, microscopic and rheological techniques. It occurs sharply at a concentration of 3.2M ammonium sulphate and is not observed with other types of salt. Rheological measurements showed that rather than precipitating under such conditions, ocr forms a weak viscoelastic gel. Far UV circular dichroism spectra reveal that ocr does not denature in the gel phase, while near UV CD spectra suggest the formation of long, helical structures. Well resolved fibrils were observed using atomic force microscopy. They were over 1µm in length and varied between 2.6nm to 10.4nm in height, corresponding to the thickness and length of the ocr dimer. Ocr is a highly charged protein (-56e at pH 8) and is shaped like a banana. We argue that it is stabilized in specifically aggregated structures at large salt concentrations by these physical properties. Electrostatic repulsions between proteins are screened by salts, allowing proteins to approach close enough to aggregate. The charge on ocr is high enough to resist such precipitation. However, at 3.2M ammonium sulphate we suggest that the salt molecules bridge neighbouring ocr dimers via hydrogen bonds, connecting amino acid carboxyl groups with the ammonium groups of the salt. The banana-shaped dimers stack on top of each other, forming long helical fibrils that intertwine into a semi flexible network.
Style APA, Harvard, Vancouver, ISO itp.
47

Al-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.

Pełny tekst źródła
Style APA, Harvard, Vancouver, ISO itp.
48

Lim, 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.

Pełny tekst źródła
Streszczenie:
There is a strong need to develop a mechanical method to apply external torque to the bacterial flagellar motor. Such a method will allow us to probe the behaviour of the motor at a range of different speeds under different external conditions. In this thesis, I explored various methods to deliver torque at the single-molecule level, in particular the use of angular optical trapping and magnetic tweezers. I have identified rutile particles as suitable handles for use in angular optical trapping due to their high birefringence. Further progress was not achieved using angular optical trapping due to the lack of a suitable method to attach birefringent particles to the bacterial flagellar motor. On the other hand, I was able to make further progress using magnetic tweezers. A highly-reproducible and high-yielding magnetic bead assay was developed along with electromagnets capable of generating fast-rotating magnetic fields at magnitudes on the order of tens of mT. Using the system of delivering magnetic torque developed, I was able to stall and rotate the motor forward at speeds up to 220 Hz and in the reverse direction. Stalling experiments carried out on the motor revealed the stator mechanosensing depends on torque and not rotation. Signatures of stators dropping out at low load experiments further confirm the load dependence of stators.
Style APA, Harvard, Vancouver, ISO itp.
49

Nauseef, Jones Trevor. "An investigation of the molecular and biophysical properties of metastatic cells". Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/3150.

Pełny tekst źródła
Streszczenie:
Prostate cancer presents a significant paradox: it is very common, yet rarely fatal. To wit, the prostate is the most common non-skin tissue for cancer diagnosis in men in the United States. Despite its high incidence, fatal malignancy occurs in only a small fraction of diagnosed men. The fatal cases are characteristically defined by distant spread in the body, also known as metastasis. In order to metastasize a cancer cell must complete several sequential steps. These include degradation of and invasion through the epithelial basement membrane, typically through the loss of static intracellular adhesions with fellow epithelial cells; entrance into the blood stream (intravasation); survival within circulation; exit from the blood stream upon arrival at a new tissue (extravasation); and survival and colonization at the secondary site. At the time of diagnosis, it is not currently possible to accurately predict future metastasis and thereby clinicians cannot delineate those men at high risk for fatal disease from the vast majority of men who are likely to experience an indolent disease course. Consequently, we examined the behavior of cancer cells in several steps of the metastatic cascade. In doing so, we uncovered both molecular and biophysical characteristics of cancer cells that may facilitate successful metastatic dissemination and tumor outgrowth. Epithelial-to-mesenchymal transition (EMT) is physiological process of transdifferentiation that is normally initiated during vertebrate development, but has recently been implicated in tumor development, progression, and metastases. The EMT program results in dramatic changes, including the exchange of epithelial for mesenchymal markers, altered cellular morphology, and gain of motility. EMT-like cellular alterations have been implicated most strongly in the metastasis steps of invasion and survival of cells at primary tumors sites. How EMT-like changes may facilitate survival and growth in the microenvironment of a micrometastatic niche has been less clearly elucidated. Consequently, we evaluated how EMT-like changes may affect the survival and subsequent outgrowth of prostate cancer cell lines following restrictive growth conditions. We observed that EMT-like cells as compared to their more epithelial counterparts displayed enhanced maintenance of their proliferative potential following extended culture in nutrient restriction. This phenotype depended on an EMT-associated increase in autophagy. Notably, the post-stress outgrowth phenotype could be conferred through a paracrine signaling mechanism that may involve autophagy-derived exosome-like extracellular vesicles. These studies demonstrated that EMT-like cells have a resistance to nutrient restriction through enhanced autophagy and may have uncovered a novel autophagy-dependent exosomal secretion pathway. Metastatic efficiency is thought to be strongly limited by the destruction of circulating tumor cells by the hemodynamic shear forces within the vasculature. However, such a persistent belief has little appropriate published experimental evidence. We developed an in vitro assay to expose cells to fluid shear stress (FSS). By monitoring the viability of the cells, we determined that transformed cells had a highly conserved ability to resist even very high FSS. The mechanism depended on the capacity to patch membrane defects, extracellular calcium, and a dynamic cytoskeleton. We also observed a stiffening of cancer cell membranes after exposure to FSS. Taken together, these studies expand the understanding of how cancer cells survive in circulation and indicate that metastatic efficiency is less limited by hemodynamic forces than previously thought. The steps of hematogenous metastasis between intravasation and extravasation necessitate the existence of circulating tumor cells (CTCs). Collection, enumeration, and study of CTCs have the potential to serve as a "liquid biopsy" of the metastatic cascade. In prostate cancer, the enumeration of CTCs by detection of the expression of epithelial markers has displayed limited clinical utility. We hypothesized that the prognostic value of CTC number may be enhanced by detection of cells which have undergone the pro-metastatic EMT-like program. We developed a flow cytometry-based experimental assay for enumeration of CTCs using epithelial (EpCAM) and mesenchymal-like (N-cadherin) surface proteins. We detected from prostatectomy patients before and after surgery events expressing EpCAM, N-cadherin, and both. However, the detection of background events from healthy control subjects was unacceptably high. These studies support the idea of mesenchymal-like tumor cells in circulation, but will require further assay development for reliable conclusions to be drawn. In sum, the work described above has provided descriptive and mechanistic insight to molecular and biophysical properties that may facilitate prostate cancer metastasis. It is our hope that these data will result in the development of relevant preventative, diagnostic, and therapeutic clinical strategies for prostate cancer.
Style APA, Harvard, Vancouver, ISO itp.
50

Costa, 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.

Pełny tekst źródła
Streszczenie:
Made available in DSpace on 2014-06-11T19:22:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-24Bitstream added on 2014-06-13T18:49:56Z : No. of bitstreams: 1 costa_lc_me_sjrp_parcial.pdf: 205173 bytes, checksum: bf8330ba8ebec2e33d2e94ec3f85ca8c (MD5) Bitstreams deleted on 2015-06-25T13:01:07Z: costa_lc_me_sjrp_parcial.pdf,. Added 1 bitstream(s) on 2015-06-25T13:03:25Z : No. of bitstreams: 1 000624262_20151231.pdf: 180856 bytes, checksum: 0c0db07749af7e17dd04bbdebcc70b88 (MD5) Bitstreams deleted on 2016-01-04T10:26:22Z: 000624262_20151231.pdf,. Added 1 bitstream(s) on 2016-01-04T10:28:15Z : No. of bitstreams: 1 000624262.pdf: 814952 bytes, checksum: c2e88a5f2759a15bbe1e835ebd0266af (MD5)
Coordenação 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)
Style APA, Harvard, Vancouver, ISO itp.
Możesz być także zainteresowany bibliografiami na temat „Moleculor Biophysics” dla innych typów źródeł:
Artykuły w czasopismach Książki
Oferujemy zniżki na wszystkie plany premium dla autorów, których prace zostały uwzględnione w tematycznych zestawieniach literatury. Skontaktuj się z nami, aby uzyskać unikalny kod promocyjny!

Do bibliografii