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1
Simons, Kim T. "Deciphering the protein folding code : ab initio prediction of protein structure /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/9234.
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Sapsaman, Temsiri. "An energy landscaping approach to the protein folding problem." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/31637.
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Thesis (Ph.D)--Mechanical Engineering, Georgia Institute of Technology, 2010.Committee Chair: Harvey Lipkin; Committee Member: Joel S. Sokol; Committee Member: Michael J. Leamy; Committee Member: Nader Sadegh; Committee Member: Stephen C. Harvey. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Kim, Junghwa. "Roles of intermediate conformation and transient disulfide bonding on native folding of P22 tailspike protein." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file 2.50 Mb., 176 p, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3220719.
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Duan, Jianxin. "Protein folding, stability and recognition /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-098-2/.
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Lundell, Sandra J. "Quantum Mechanical Studies of N-H···N Hydrogen Bonding in Acetamide Derivatives and Amino Acids." DigitalCommons@USU, 2018. https://digitalcommons.usu.edu/etd/7309.
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Proteins are made of vast chains of amino acids that twist and fold into intricate designs. These structures are held in place by networks of noncovalent interactions. One of these, the hydrogen bond, forms bridges between adjacent pieces of the protein chain and is one of the most important contributors to the shape and stability of proteins. Hydrogen bonds come in all shapes and sizes and a full understanding of these not only aids in our understanding of proteins in general but can bridge the gap to finding cures to many protein-related diseases, such as sickle-cell anemia. The primary aim of this thesis is to discover if a specific type of hydrogen bond, the N-H···N bond, occurs within proteins and if so, if it contributes to the structure and stability of proteins.
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English, William R. "Effects of calcium on conformation and stability of porcine pancreatic phospholipase Aâ†2." Thesis, University of Kent, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285981.
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Phan, Jamie. "Investigating protein folding by the de novo design of an α-helix oligomer." Scholarly Commons, 2013. https://scholarlycommons.pacific.edu/uop_etds/859.
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Proteins are composed of a unique sequence of amino acids, whose order guides a protein to adopt its particular fold and perform a specific function. It has been shown that a protein's 3-dimensional structure is embedded within its primary sequence. The problem that remains elusive to biochemists is how a protein's primary sequence directs the folding to adopt such a specific conformation. In an attempt to gain a better understanding of protein folding, my research tests a novel model of protein packing using protein design. The model defines the knob-socket construct as the fundamental unit of packing within protein structure. The knob-socket model characterizes packing specificity in terms of amino acid preferences for sockets in different environments: sockets filled with a knob are involved in inter-helical interactions and free sockets are involved in intra-helical interactions. Equipped with this knowledge, I sought to design a unique protein, Ksα1.1, completely de novo. The sequence was selected to induce helix formation with a predefined tertiary packing interface. Circular dichroism showed that Ksα1.1 formed α-helical secondary structure as intended. The nuclear magnetic resonance studies demonstrated formation of a high order oligomer with increased protein concentration. These results and analysis prove that the knob-socket model is a predictive model for all α-helical protein packing. More importantly, the knob-socket model introduces a new protein design method that can potentially hold a solution to the folding problem.
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Phan, Jamie. "Investigating protein folding by the de novo design of an α-helix oligomer : a thesis." Scholarly Commons, 2001. https://scholarlycommons.pacific.edu/uop_etds/859.
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Proteins are composed of a unique sequence of amino acids, whose order guides a protein to adopt its particular fold and perform a specific function. It has been shown that a protein's 3-dimensional structure is embedded within its primary sequence. The problem that remains elusive to biochemists is how a protein's primary sequence directs the folding to adopt such a specific conformation. In an attempt to gain a better understanding of protein folding, my research tests a novel model of protein packing using protein design. The model defines the knob-socket construct as the fundamental unit of packing within protein structure. The knob-socket model characterizes packing specificity in terms of amino acid preferences for sockets in different environments: sockets filled with a knob are involved in inter-helical interactions and free sockets are involved in intra-helical interactions. Equipped with this knowledge, I sought to design a unique protein, Ksα1.1, completely de novo. The sequence was selected to induce helix formation with a predefined tertiary packing interface. Circular dichroism showed that Ksα1.1 formed α-helical secondary structure as intended. The nuclear magnetic resonance studies demonstrated formation of a high order oligomer with increased protein concentration. These results and analysis prove that the knob-socket model is a predictive model for all α-helical protein packing. More importantly, the knob-socket model introduces a new protein design method that can potentially hold a solution to the folding problem.
9
Devlin, Glyn L. "The mechanisms of serpin misfolding and its inhibition." Monash University, Dept. of Biochemistry and Molecular Biology, 2003. http://arrow.monash.edu.au/hdl/1959.1/9469.
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Chen, Chong. "Investigating Nonnative Contacts in Protein Folding." University of Akron / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=akron1238087880.
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Tjernberg, Agneta. "Protein mass spectrometry in the drug discovery process /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-251-9/.
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Mackness, Brian C. "The Identification and Targeting of Partially-Folded Conformations on the Folding Free-Energy Landscapes of ALS-Linked Proteins for Therapeutic Intervention: A Dissertation." eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/826.
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The hallmark feature of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), is the accumulation of cytoplasmic inclusions of key disease-linked proteins. Two of these proteins, TDP-43 and SOD1, represent a significant proportion of sporadic and familial ALS cases, respectively. The population of potentially aggregation-prone partially-folded states on the folding free-energy landscape may serve as a common mechanism for ALS pathogenesis. A detailed biophysical understanding of the folding and misfolding energy landscapes of TDP-43 and SOD1 can provide critical insights into the design of novel therapeutics to delay onset and progression in ALS.
Equilibrium unfolding studies on the RNA recognition motif (RRM) domains of TDP-43 revealed the population of a stable RRM intermediate in RRM2, with residual structure localized to the N-terminal half of the domain. Other RRM domains from FUS/TLS and hnRNP A1 similarly populate RRM intermediates, suggesting a possible connection with disease. Mutations, which enhance the population of the RRM2 intermediate, could serve as tools for deciphering the functional and misfolding roles of this partially-folded state in disease models, leading to the development of new biomarkers to track ALS progression.
ALS mutations in SOD1 have been shown to destabilize the stable homodimer to result in increased populations of the monomeric and unfolded forms of SOD1. Mechanistic insights into the misfolding of SOD1 demonstrated that the unfolded state is a key species in the initiation and propagation of aggregation, suggesting that limiting these populations may provide therapeutic benefit to ALS patients. An in vitro time-resolved Förster Resonance Energy Transfer assay to screen small molecules that stabilize the native state of SOD1 has identified several lead compounds, providing a pathway to new therapeutics to treat ALS.
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Mackness, Brian C. "The Identification and Targeting of Partially-Folded Conformations on the Folding Free-Energy Landscapes of ALS-Linked Proteins for Therapeutic Intervention: A Dissertation." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/826.
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The hallmark feature of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), is the accumulation of cytoplasmic inclusions of key disease-linked proteins. Two of these proteins, TDP-43 and SOD1, represent a significant proportion of sporadic and familial ALS cases, respectively. The population of potentially aggregation-prone partially-folded states on the folding free-energy landscape may serve as a common mechanism for ALS pathogenesis. A detailed biophysical understanding of the folding and misfolding energy landscapes of TDP-43 and SOD1 can provide critical insights into the design of novel therapeutics to delay onset and progression in ALS.
Equilibrium unfolding studies on the RNA recognition motif (RRM) domains of TDP-43 revealed the population of a stable RRM intermediate in RRM2, with residual structure localized to the N-terminal half of the domain. Other RRM domains from FUS/TLS and hnRNP A1 similarly populate RRM intermediates, suggesting a possible connection with disease. Mutations, which enhance the population of the RRM2 intermediate, could serve as tools for deciphering the functional and misfolding roles of this partially-folded state in disease models, leading to the development of new biomarkers to track ALS progression.
ALS mutations in SOD1 have been shown to destabilize the stable homodimer to result in increased populations of the monomeric and unfolded forms of SOD1. Mechanistic insights into the misfolding of SOD1 demonstrated that the unfolded state is a key species in the initiation and propagation of aggregation, suggesting that limiting these populations may provide therapeutic benefit to ALS patients. An in vitro time-resolved Förster Resonance Energy Transfer assay to screen small molecules that stabilize the native state of SOD1 has identified several lead compounds, providing a pathway to new therapeutics to treat ALS.
14
Zhang, Wei. "Computational simulation of biological systems studies on protein folding and protein structure prediction /." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file 2.84Mb, 184 p, 2005. http://wwwlib.umi.com/dissertations/fullcit/3181881.
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Botelho, Hugo M. "Metal ions and protein folding: conformational and functional interplay." Doctoral thesis, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, 2010. http://hdl.handle.net/10362/5151.
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Dissertation presented to obtain a PhD degree in Biochemistry at Instituto de Tecnologia Química e Biológica, Universidade Nova de LisboaMetal ions are cofactors in about 30% of all proteins, where they fulfill catalytical and structural roles. Due to their unique chemistry and coordination properties they effectively expand the intrinsic polypeptide properties (by participating in catalysis or electron transfer reactions), stabilize protein conformations (like in zinc fingers) and mediate signal transduction (by promoting functionally relevant protein conformational changes). However, metal ions can also exert have deleterious effects in living systems by incorporating in non-native binding sites, promoting aberrant protein aggregation or mediating redox cycling with generation of reactive oxygen and nitrogen species. For this reason, the characterization of the roles of metal ions as modulators of protein conformation and stability provides fundamental knowledge on protein folding properties and is instrumental in establishing the molecular basis of disease. In this thesis we have analyzed protein folding processes using model protein systems incorporating covalently bound metal cofactors – iron-sulfur (FeS) proteins – or where metal ion binding is reversible and associated conformational readjustments – the S100 proteins.(...)
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Aguilar, Ximena. "Folding and interaction studies of subunits in protein complexes." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84726.
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Proteins function as worker molecules in the cell and their natural environment is crowded. How they fold in a cell-like environment and how they recognize their interacting partners in such conditions, are questions that underlie the work of this thesis. Two distinct subjects were investigated using a combination of biochemical- and biophysical methods. First, the unfolding/dissociation of a heptameric protein (cpn10) in the presence of the crowding agent Ficoll 70. Ficoll 70 was used to mimic the crowded environment in the cell and it has been used previously to study macromolecular crowding effects, or excluded volume effects, in protein folding studies. Second, the conformational changes upon interaction between the Mediator subunit Med25 and the transcription factor Dreb2a from Arabidopsis thaliana. Mediator is a transcriptional co-regulator complex which is conserved from yeast to humans. The molecular mechanisms of its action are however not entirely understood. It has been proposed that the Mediator complex conveys regulatory signals from promoter-bound transcription factors (activators/repressors) to the RNA polymerase II machinery through conformational rearrangements. The results from the folding study showed that cpn10 was stabilized in the presence of Ficoll 70 during thermal- and chemical induced unfolding (GuHCl). The thermal transition midpoint increased by 4°C, and the chemical midpoint by 0.5 M GuHCl as compared to buffer conditions. Also the heptamer-monomer dissociation was affected in the presence of Ficoll 70, the transition midpoint was lower in Ficoll 70 (3.1 μM) compared to in buffer (8.1 μM) thus indicating tighter binding in crowded conditions. The coupled unfolding/dissociation free energy for the heptamer increased by about 36 kJ/mol in Ficoll. Altogether, the results revealed that the stability effect on cpn10 due to macromolecular crowding was larger in the individual monomers (33%) than at the monomer-monomer interfaces (8%). The results from the interaction study indicated conformational changes upon interaction between the A. thaliana Med25 ACtivator Interaction Domain (ACID) and Dreb2a. Structural changes were probed to originate from unstructured Dreb2a and not from the Med25-ACID. Human Med25-ACID was also found to interact with the plant-specific Dreb2a, even though the ACIDs from human and A. thaliana share low sequence homology. Moreover, the human Med25-interacting transcription factor VP16 was found to interact with A. thaliana Med25. Finally, NMR, ITC and pull-down experiments showed that the unrelated transcription factors Dreb2a and VP16 interact with overlapping regions in the ACIDs of A. thaliana and human Med25. The results presented in this thesis contribute to previous reports in two different aspects. Firstly, they lend support to the findings that the intracellular environment affects the biophysical properties of proteins. It will therefore be important to continue comparing results between in vitro and cell-like conditions to measure the magnitude of such effects and to improve the understanding of protein folding and thereby misfolding of proteins in cells. Better knowledge of protein misfolding mechanisms is critical since they are associated to several neurodegenerative diseases such as Alzheimer’s and Parkinson's. Secondly, our results substantiate the notion that transcription factors are able to bind multiple targets and that they gain structure upon binding. They also show that subunits of the conserved Mediator complex, despite low sequence homologies, retain a conserved structure and function when comparing evolutionary diverged species.
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Smith, Nathan B. "Computational Studies of Protein Folding Assistance and Conformational Pathways of Biological Nanomachines." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1448037580.
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Gillespie, D. Blake. "Conformational dynamics and intermediates in the folding pathway of T4 lysozyme /." view abstract or download file of text, 1999. http://wwwlib.umi.com/cr/uoregon/fullcit?p9957566.
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Thesis (Ph. D.)--University of Oregon, 1999.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 101-110). Also available for download via the World Wide Web; free to University of Oregon users. Address: http://wwwlib.umi.com/cr/uoregon/fullcit?p9957566.
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Hagarman, Andrew Michael Schweitzer-Stenner Reinhard. "Conformations of unfolded and partially folded peptides and proteins probed by optical spectroscopy /." Philadelphia, Pa. : Drexel University, 2010. http://hdl.handle.net/1860/3313.
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Syed, Ali Abbas Razvi. "A comparative study of HPr proteins from extremophilic organisms." Texas A&M University, 2005. http://hdl.handle.net/1969.1/3163.
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A thermodynamic study of five homologous HPr proteins derived from organisms
inhabiting diverse environments has been undertaken. The aim of this study was to further
our understanding of protein stabilization in extremes of environment. Two of the proteins
were derived from moderate thermophiles (Streptococcus thermophilus and Bacillus
staerothermophilus) and two from haloalkaliphilic organisms (Bacillus halodurans and
Oceanobacillus iheyensis); these proteins were compared with HPr from the mesophile Bacillus
subtilus. Genes for three of these homologous HPr proteins were for the first time cloned
from their respective organisms into expression vectors and they were over-expressed and
purified in Escherichia coli. Stability measurements were performed on these proteins under a
variety of solution conditions (varying pH, salinity and temperature) by thermal and solvent
induced denaturation experiments. Stability curves were determined for every homologue
and these reveal very similar conformational stability for these homologues at their
habitat temperatures. The BstHPr homologue is the most thermostable and also has the
highest G25; the stability of other homologues was ranked as Bst>Bh>St>Bs>OiHPr.
Other key thermodynamic parameters, like Cp, have been estimated for all the homologues and it was found that these values are identical within errors of estimation. Also, it was found that the values of TS are very similar for these homologues. Together these observations allow us to propose a thermodynamic mechanism toward achieving higher Tm. The crystal structures of the BstHPr and a single tryptophan-containing variant (BstF29W) of this homologue are also reported here. Also reported is a domain-swapped dimeric structure for the BstF29W variant, together with a detailed investigation into the
solution oligomeric nature of this protein. The crystal structure of BstHPr is analyzed to
enumerate various stabilizating interactions like hydrogen bonds and salt-bridges and these were compared with those for the mesophilic homologue BsHPr. Finally, an analysis of sequence alignments together with structural information for these homologues has allowed design of numerous variants of both Bs and BstHPr. A detailed thermodynamic study of
these variants is presented in an attempt to understand the origins of the differences in
stability of the HPr homologues.
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Hoang, Huy Ngoc. "Metal clips for folding peptides : a study of palladium (II) binding to histidine residues in short peptides stabilize (sic) their a-Helical conformation in solutions /." St. Lucia, Qld, 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17478.pdf.
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Wang, Zijian. "Single-Molecule Spectroscopy And Imaging Studies Of Protein Folding-Unfolding Conformational Dynamics: The Multiple-State And Multiple-Channel Energy Landscape." Bowling Green State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1459942296.
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Chen, Wei. "Molecular dynamics simulations of binding, unfolding, and global conformational changes of signaling and adhesion molecules." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28118.
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Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2009.Committee Chair: Zhu, Cheng; Committee Member: Harvey, Stephen; Committee Member: Hud, Nicholas; Committee Member: Zamir, Evan; Committee Member: Zhu, Ting.
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Lundqvist, Martin 1972. "Conformations of polypeptides at nanoparticles interfaces : protein structural changes and induced folding of peptides /." Linköping : Dept. of Physics and Measurement Technology, Biology and Chemistry, Univ, 2005. http://www.bibl.liu.se/liupubl/disp/disp2005/tek926s.pdf.
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Zych, Andrew John. "Conformational characterization of abiotic secondary structure based on aromatic stacking /." Full text (PDF) from UMI/Dissertation Abstracts International, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3008484.
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Caravella, Justin Andrew 1974. "Electrostatics and packing in biomolecules : accounting for conformational change in protein folding and binding." Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/16823.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2002.Includes bibliographical references (p. 189-205).
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
The role of electrostatics and packing in protein folding and molecular association was assessed in different biomolecular systems. A continuum electrostatic model was applied to long-range electrostatic effects in the binding of human carbonic anhydrase II to a sulfonamide inhibitor. The effect of chemically modifying lysine e-amino groups was computed, and the average calculated value showed good agreement with experimental results determined by capillary electrophoresis. In a second study, the continuum model was used to analyze all the electrostatic interactions in the Zif268 protein-DNA complex. The net electrostatic effect was unfavorable to binding, although many individual groups or group pairs had a favorable effect, and the residues most unfavorable to binding correspond to those thought to be important for specificity. Also, a measure of electrostatic complementarity was developed and applied to myoglobin-both to known sequences and to hypothetical chimeric myoglobin sequences. The complementarity measure rated the correct myoglobins higher than chimeric myoglobins when crystal structures were used, and performed better than other readily available measures of complementarity when myoglobin homology models were evaluated. In the second part of the thesis, methods for repacking proteins were presented and applied to Arc repressor. Sequence variants that are predicted to fold as heterodimers preferentially and variants that favor a switch-Arc structure over wild-type were found.
(cont.) In a final set of calculations, the search algorithms for repacking were combined with electrostatic effects predicted from an approximate continuum model. The structure of Zif268 zinc finger 1 complexed to DNA was predicted when limited docking and side chain flexibility were allowed. The predicted structure shows good agreement with the x-ray crystal structure. A second repacked structure provides insight into how sequence changes affect structure and hence binding specificity in the zinc finger protein.
by Justin Andrew Caravella.
Ph.D.
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Tripathi, Swarnendu. "Conformational Transition Mechanisms of Flexible Proteins." Kent State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1281491004.
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Wengler, Daniela [Verfasser], and Don C. [Akademischer Betreuer] Lamb. "Conformational changes of proteins involved in the chaperone mediated protein folding cycle measured by spFRET / Daniela Wengler ; Betreuer: Don C. Lamb." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2016. http://d-nb.info/1124779914/34.
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Wan, Hongbin. "Efficient sampling of protein conformational dynamics and prediction of mutation effects." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/575951.
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ChemistryPh.D.
Molecular dynamics (MD) simulation is a powerful tool enabling researchers to gain insight into biological processes at the atomic level. There have been many advancements in both hardware and software in the last decade to both accelerate MD simulations and increase their predictive accuracy; however, MD simulations are typically limited to the microsecond timescale, whereas biological motions can take seconds or longer. Because of this, it remains extremely challenging to restrain simulations using ensemble-averaged experimental observables. Among various approaches to elucidate the kinetics of molecular simulations, Markov State Models (MSMs) have proven their ability to extract both kinetic and thermodynamic properties of long-timescale motions using ensembles of shorter MD simulation trajectories. In this dissertation, we have implemented an MSM path-entropy method, based on the idea of maximum-caliber, to efficiently predict the changes in protein folding behavior upon mutation. Next, we explore the accuracy of different MSM estimators applied to trajectory data obtained by adaptive seeding, in which new rounds of short MD simulations are collected from states of interest, and propose a simple method to build accurate models by population re-weighting of the transition count matrix. Finally, we explore ways to reconcile simulated ensembles with Hydrogen/Deuterium exchange (HDX) protection measurements, by constructing multi-ensemble Markov State Models (MEMMs) from biased MD simulations, and reconciling these predictions against the experimental data using the BICePs (Bayesian Inference of Conformational Populations) algorithm. We apply this approach to model the native-state conformational ensemble of apomyoglobin at neutral pH.
Temple University--Theses
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Zhou, Guangfeng. "STATISTICAL MODELS AND THEIR APPLICATIONS IN STUDYING BIOMOLECULAR CONFORMATIONAL DYNAMICS." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/478773.
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ChemistryPh.D.
It remains a major challenge in biophysics to understand the conformational dynamics of biomolecules. As powerful tools, molecular dynamics (MD) simulations have become increasingly important in studying the full atomic details of conformational dynamics of biomolecules. In addition, many statistical models have been developed to give insight into the big datasets from MD simulations. In this work, I first describe three statistical models used to analyze MD simulation data: Lifson-Roig Helix-Coil theory, Bayesian inference models, and Markov state models. Then I present the applications of each model in analyzing MD simulations and revealing insight into the conformational dynamics of biomolecules. These statistical models allow us to bridge microscopic and macroscopic mechanisms of biological processes and connect simulations with experiments.
Temple University--Theses
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Wirmer, Julia. "Investigation of the kinetics of protein folding and the ensemble of conformations in non-native states of proteins by liquid NMR spectroscopy." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/32425.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.Vita.
Includes bibliographical references (p. 187-202).
For a complete description of protein folding dynamics and the structure of the folded state, of unfolded and of non-native states of proteins and the kinetics of protein folding from the unfolded state to the folded state have to be determined. The focus of this PhD thesis was the development of novel NMR methodologies to study protein folding using NMR spectroscopy. This has been achieved by studying three model proteins ubiquitin, [alpha]-lactalbumin and lysozyme in their folded and especially in their unfolded states. The proteins were chosen, because [alpha]-lactalbumin and lysozyme are two proteins with nearly identical fold but different function and ubiquitin is a very stable protein without disulfide bonds. Methodologies A new NMR pulse sequence for the determination of ... and ... coupling constants in proteins was developped. The method is based on J-modulated HSQCs and can be applied to folded as well as unfolded proteins. The new coupling constants report on backbone [phi] and [psi] angles. . Residual structure and long-range interactions in unfolded proteins can be detected by a new combination of site directed non-conservative mutagenesis and NMR analysis. Identification of long-range interactions is a) based on the analysis and interpretation of R₂ relaxation rates, for which models have been derived and b) based on NMR diffusion data which directly correlate to the compactness of a given protein. A method to study laser triggered kinetics of protein folding by time-resolved photo- CIDNP NMR was developed. Two lasers were coupled into an NMR spectrometer:
(cont.) one for initiation of folding by releasing ions from photo-labile chelators with dead times as low as 200ms, and one for induction of photo-CINDP NMR. The method can not only be applied to ion induced kinetics of protein folding, but is generally applicable to kinetics of biomacromolecules such as proteins and RNA that involve photo-protected cofactors as could be shown in our laboratory. Investigations on ubiquitin The newly developed NMR method for the determination of ... and ... coupling constants was applied to folded ubiquitin. Analysis revealed the dependence of the coupling constants on the backbone conformation, predominantly on [psi], making the pulse sequence and the parameterization developed here a valuable new tool for the determination of the backbone conformation in folded as well as in unfolded proteins. Unfolded ubiquitin was investigated using scalar coupling constants and ¹H,¹⁵N relaxation data. The experimental data agree well with models proposed to describe unfolded states of proteins as a statistical coil where dynamics are governed solely by segmental motions. Unfolded ubiquitin is thus a good model for a protein without detectable residual structure in its unfolded state. Investigations on lysozyme Residual structure in the unfolded states of non conservative single point mutants (A9G, W62G, W62Y, W 1 1G and W123G) of hen lysoszyme was monitored by chemical shift measurements, ¹⁵N transverse relaxation rates and particularly diffusion constants. Long- range interactions between hydrophobic clusters of unfolded lysozyme were observed. Single point mutations dramatically alter the overall compactness of the unfolded state.
(cont.) Investigations on [alpha]-lactalbumin · Isotope labeled bovine [alpha]-lactalbumin (BLA) was expressed heterologously using a new construct with a His-tag and a trypsin cleavage site. The sequence and stability of the obtained BLA is identical to the wild type protein. This makes it a perfect construct to study kinetics of folding and unfolded states of BLA. ¹³C,¹⁵N isotope labeled unfolded BLA was assigned applying standard and non-standard NMR assignment experiments. Residual secondary structure was identified near the N- and the C-terminus of unfolded BLA, in regions belonging to the -domain in the folded state, suggesting a possible folding nucleus. · This unfolded state of BLA was furthermore compared to the unfolded state of human lactalbumin (HLA) and lysozyme based on residual structure and ¹⁵N relaxation data. The unfolded states vary considerably for the three proteins, which possess very similar structures in their native state. The structural ensemble in the unfolded states of proteins are determined by the primary sequence of the protein and even smallest single point mutations as found between HLA and BLA can change the conformation of the unfolded state considerably. · The Ca²⁺-triggered folding kinetics of BLA under constant denaturant (4M urea) has been investigated by laser induced release of Ca²⁺-ions from a photolabile chelator within the NMR spectrometer and subsequent photo-CIDNP signal detection. A folding intermediate possessing a tyrosine residue in a non-native conformation was detected 200ms after initiation of folding. Therefore, parts of the polypeptide chain in the [beta]-domain of BLA sample non-native conformations, while a hydrophobic core is formed.
(cont.) The findings in the kinetic investigations are in line with the detected residual structure. Refolding of amino acids involved in non-native clusters in the intermediates has to proceed the correct folding and therefore constitutes a rate limiting step on the Ca²⁺-induced refolding of [alpha]- lactalbumin.
by Julia Wirmer.
Ph.D.
32
Kalapothakis, Jason Michael Drosos. "Investigations of peptide structural stability in vacuo." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/5670.
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Gas-phase analytical techniques provide very valuable tools for tackling the structural complexity of macromolecular structures such as those encountered in biological systems. Conformational dynamics of polypeptides and polypeptide assemblies underlie most biological functionalities, yet great difficulties arise when investigating such phenomena with the well-established techniques of X-ray crystallography and NMR. In areas such as these ion mobility interfaced with mass spectrometry (IMMS) and molecular modelling can make a significant contribution. During an IMMS experiment analyte ions drift in a chamber filled with an inert gas; measurement of the transport properties of analyte ions under the influence of a weak electric field can lead to determination of the orientationally-averaged collision cross-section of all resolved ionic species. A comparison with cross-sections estimated for model molecular geometries can lead to structural assignments. Thus IMMS can be used effectively to separate gas-phase ions based on their conformation. The drift tube employed in the experiments described herein is thermally regulated, which also enables the determination of collision cross-sections over a range of temperatures, and can provide a view of temperature-dependent conformational dynamics over the experimental (low microsecond) timescale. Studies described herein employ IMMS and a gamut of other MS-based techniques, solution spectroscopy and – importantly – molecular mechanics simulations to assess a) conformational stability of isolated peptide ions, with a focus on small model peptides and proteins, especially the Trp cage miniprotein; and b) structural characteristics of oligomeric aggregates of an amyloidogenic peptide. The results obtained serve to clarify the factors which dominate the intrinsic stability of non-covalent structure in isolated peptides and peptide assemblies. Strong electrostatic interactions are found to play a pivotal role in determining the conformations of isolated proteins. Secondary structures held together by hydrogen bonding, such as helices, are stable in the absence of solvent, however gas-phase protein structures display loss of their hydrophobic cores. The absence of a polar solvent, “self-solvation” is by far the most potent force influencing the gas-phase configuration of these systems. Geometries that are more compact than the folded state observed in solution are routinely detected, indicating the existence of intrinsically stable compact non-native states in globular proteins, illuminating the nature of proteins’ ‘unfolded’ states.
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Subramaniam, Srisunder. "Studies of conformational changes and dynamics accompanying substrate recognition, allostery and catalysis in bacteriophage lambda integrase." The Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111655332.
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Gerlach, Lisa [Verfasser]. "BamB facilitates folding of outer membrane protein A (OmpA) via interactions of its β-propeller with the membrane surface and via a conformation change induced by phosphatidylglycerol / Lisa Gerlach." Kassel : Universitätsbibliothek Kassel, 2020. http://d-nb.info/1204016488/34.
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Ujma, Jakub. "Development and use of novel instrumentation for structural analysis of gaseous ions." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/development-and-use-of-novel-instrumentation-for-structural-analysis-of-gaseous-ions(7c299a20-a306-4851-85de-5d2827bc549e).html.
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Traditional solution and solid state approaches (Nuclear Magnetic Resonance, X-Ray Crystallography) are methods of choice when analysing both biological and inorganic analytes. However, the characterisation of transient species, often encountered in self-assembling systems, is difficult. Such systems rarely produce crystals of high quality and due to their dynamic nature; their structures are difficult to study with NMR. Hyphenated gas phase methods which rely on mass spectrometry detection offer simultaneous structural analysis and direct stoichiometry measurement. As a consequence, it is possible to investigate specific, non-interacting molecules and molecular complexes in an isolated environment. This thesis focuses on the development and applications of two such methods - ion mobility mass spectrometry (IM-MS) and cold ion spectroscopy. IM-MS measurements yield a so called collisional cross sectional area (CCS). This parameter can be pictured as a rotationally averaged, shadow projection of a molecule structure. When correlated with the ion abundance, a CCS distribution yields intuitively interpretable information about the conformational preferences of an isolated molecule. Although indispensable in describing a "global" geometrical structure, the CCS parameter itself provides a limited insight into the local structural features of the assembly. Ion spectroscopy, both in the UV and IR regions, can provide an extra layer of highly descriptive information. Here, we present several cases where the above techniques have been applied. With the aid of IM-MS, we have analysed the geometry of inorganic supramolecular assemblies, highlighting the stability of particular metal-ligand interactions. Using cold ion spectroscopy, we have assessed the fine structural information of self-assembled oligomers of an amyloidogenic peptide. We correlated spectral features of isolated oligomers to features observed in the mature fibrils; therefore attempting to delineate the events in early stages of amyloidogenic aggregation. A major part of this report focusses on technological aspects of the design and development of a high resolution, variable temperature ion mobility mass spectrometer (VT-IM-MS). The thermal stability of molecules is a vital aspect in industrial process development and formulation science. Solution phase Differential Scanning Calorimetry (DSC) is a widely applied technique, allowing to monitor reversibility of thermally induced conformational transitions, a key aspect in protein folding analysis. The instrument reported here aims to provide parallel information about gaseous ions, with a particular focus on protein ions. Capabilities of the newly built instrument have been tested using small, rigid molecules, a small protein and a large multiprotein complex.
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Marahatta, Ram Prasad. "Folding of Bovine Pancreatic Trypsin Inhibitor (BPTI) is Faster using Aromatic Thiols and their Corresponding Disulfides." FIU Digital Commons, 2017. https://digitalcommons.fiu.edu/etd/3530.
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Improvement in the in vitro oxidative folding of disulfide-containing proteins, such as extracellular and pharmaceutically important proteins, is required. Traditional folding methods using small molecule aliphatic thiol and disulfide, such as glutathione (GSH) and glutathione disulfide (GSSG) are slow and low yielding. Small molecule aromatic thiols and disulfides show great potentiality because aromatic thiols have low pKa values, close to the thiol pKa of protein disulfide isomerase (PDI), higher nucleophilicity and good leaving group ability. Our studies showed that thiols with a positively charged group, quaternary ammonium salts (QAS), are better than thiols with negatively charged groups such as phosphonic acid and sulfonic acid for the folding of bovine pancreatic trypsin inhibitor (BPTI). An enhanced folding rate of BPTI was observed when the protein was folded with a redox buffer composed of a QAS thiol and its corresponding disulfide.
Quaternary ammonium salt (QAS) thiols and their corresponding disulfides with longer alkyl side chains were synthesized. These QAS thiols and their corresponding disulfides are promising small molecule thiols and disulfides to fold reduced BPTI efficiently because these thiols are more hydrophobic and can enter the core of the protein.
Conformational changes of disulfide-containing proteins during oxidative folding influence the folding pathway greatly. We performed the folding of BPTI using targeted molecular dynamics (TMD) simulation and investigated conformational changes along with the folding pathway. Applying a bias force to all atoms versus to only alpha carbons and the sulfur of cysteines showed different folding pathways. The formation of kinetic traps N' and N* was not observed during our simulation applying a bias force to all atoms of the starting structure. The final native conformation was obtained once the correct antiparallel β-sheets and subsequent Cys14-Cys38 distance were decreased to a bond distance level. When bias force was applied to only alpha carbons and the sulfur of cysteines, the distance between Cys14-Cys38 increased and decreased multiple times, a structure similar to the confirmation of N*, NSH were formed and native protein was ultimately obtained. We concluded that there could be multiple pathways of conformational folding which influence oxidative folding.
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Ginn, C. L. "Protein PEGylation on protein folding." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1403227/.
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E.coli is one of the most widely utilised hosts for protein expression due to its rapid growth, low production costs and high product yields. Often proteins are deposited as insoluble inclusion bodies that later require refolding to achieve biological activity. As a result of misfolding and aggregation for many proteins refolding is the yield limiting step in their production. Relevant therapeutic proteins obtained from E.coli include the α-helical barrel proteins (e.g. interferon-α2). Many proteins derived from E.coli are further modified after refolding by the covalent conjugation of poly(ethylene glycol) (PEG). This is known as PEGylation and several PEGylated α-helical barrel proteins are now routinely used in the clinic. PEGylation is used to address the short circulation half-life, immunogenicity and poor stability associated with many protein-based therapeutics. Our method of PEGylation is site specific. Conjugation occurs by bis-alkylation and takes advantage of the presence of the two free thiols from native disulfide bonds that have been reduced. The conjugated product has PEG linked to the protein through a three-carbon bridge spanning the two thiols derived from the native disulfide. Currently proteins are first purified and then a PEG reagent is used to covalently conjugate PEG to the protein. The PEG-protein conjugate is then purified. This means the protein has to be purified twice which can reduce yields. PEGylating the protein during its initial refolding would avoid the need of two downstream purification processes resulting in a more efficient process with an improved product yield. Therefore the aim of this project is to integrate the process of protein folding and PEGylation to make the production of PEGylated proteins more economically viable allowing their widespread use in the clinic. In this project the following hypotheses will be tested i) Reducing the number of purification steps that need to be performed to improve the overall yield of recovered protein, ii) The ability of PEG to impart the properties of a glycosyl group or a chaperone and protect the protein against aggregation during the folding process, iii) our method of PEGylation in particular should promote the formation of the protein’s disulfides bond and therefore the protein’s thermodynamically stable native state and iv) that the specificity of the conjugation can still be maintained despite the exposure of more sites of conjugation. Here we examine this process with different model alpha helical barrel proteins namely leptin, IFN-β and EPO. In each case the protein was denatured and fully reduced then refolded in the presence of a thiol specific, bis-alkylation PEG reagent allowing us to effectively capture the cysteine thiols during the refolding process. For IFN-β which is highly prone to aggregation, refolding yields in the presence of the PEG reagent were much improved suggesting that our method of PEGylation had a stabilising effect on the protein structure during refolding. This improved stability was also found to benefit the protein after PEGylation. Isolation of the purified PEGylated IFN- conjugate could be achieved in a single purification step in good yield. A similar activity to that generated on PEGylation of the fully folded protein was observed suggesting that for a protein with an accessible disulfide PEGylation did not significantly affect its folding. Some work was also carried out on RNase A and T1 which contain multiple inaccessible disulfides. In this instance PEGylation appeared to hinder the refolding process either by sterically hindering the formation of the protein’s native structure or by incorrect disulfide bond formation. The work described herein therefore suggests that it is possible to refold and PEGylate proteins within a single step but the effectiveness of this approach is likely to be protein dependant.
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López, Asamar Abraham. "Study of the conformational dynamics of prolyl oligopeptidase." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/301430.
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Prolyl oligopeptidase (POP) is an 81-KDa bidomain enzyme which hydrolyses short proline-containing peptides. This enzyme is involved in mnemonic and cognitive processes, and the dysregulation of POP activity is related to mental diseases. Probably, POP modulates the phosphoinositide signalling pathway through protein-protein interactions (PPI). Hence, the development of POP inhibitors is an area of great interest for the treatment of cognitive deficits associated with mental and neurodegenerative diseases. Recently, it has been found that the administration of POP inhibitors increases the clearance of a-synuclein aggregates in vivo, indicating that POP can be related to some extend with the pathogenic conditions of Parkinson’s disease (PD). Probably, this increase in the a-synuclein catabolism might be a consequence of a direct interaction between the two proteins. For this reason, POP inhibitors might be drug candidates for the preventive treatment of PD.
Although the X-ray structure of POP is well studied, it is not clear which are the conformational fluctuations responsible for the circulation of substrates and products during the catalytic cycle. Several studies suggest that loops surrounding the active site are involved in a gating mechanism, while others postulate that interdomain separation might expose the active site. Moreover, such conformational transitions might be essential for the recognition events of POP. The elucidation of the conformational landscape of POP is a challenging task due to the high molecular weight of the enzyme.
In this PhD thesis we have used a combination of robust biophysical tools (in particular, NMR and SAXS) together with molecular dynamics simulations (MD) in order to decipher the conformational dynamics of POP in solution. In addition, POP was also analysed by ion mobility mass spectrometry, an emerging biophysical tool in structural biology. Finally, we performed preliminary studies of the interaction between POP and a-synuclein by NMR.
The results obtained in this PhD thesis demonstrated that POP exists in solution in a slow conformational exchange between open and closed conformations. The conformational transitions involved the periodic separation of the two domains in a hinge-type motion. Relaxation dispersion experiments showed that this long range conformational transition was better described by several independent motions of different amplitudes, stressing the highly dynamic behaviour of POP. Moreover, the analysis of SAXS data complemented by MD simulations found that the interdomain separation caused the inactive arrangement of the active site. This suggests that the separation between domains might be critical for substrate recruitment and product release. Of interest, inhibitors caused the total displacement of this equilibrium towards the stabilized closed conformation, therefore quenching dynamics and the catalytic activity.
The study of the interaction between POP and a-synuclein by NMR disclosed that both proteins might be involved in a weak and transient interaction. Of interest, this interaction showed more affinity in the case of POP bound to inhibitors. In this case, interaction specially affected a broad segment of the C-terminal region of a-synuclein. This result suggested that the recognition between the two proteins depends on the conformational state of POP. Therefore, modulating the conformational landscape of POP by inhibitors might control this interaction.
In summary, the results obtained in this PhD thesis demonstrated that POP undergo slow exchange between open and closed conformations in solution, and found that inhibitors have deep effects in the native conformational landscape of POP. Of interest, these conformational transitions might be essential for regulating the PPI necessary for the biological function of POP. Hence, the in vivo effects of POP inhibitors might result as a consequence of the alterations in the recognition events of POP.La prolil oligopeptidasa (POP) es un enzim de 81 KDa que hidrolitza pèptids curts amb contingut en prolina. La POP actua en el sistema nerviós central mitjançant interaccions proteïna-proteïna (IPP), i la seva funció biològica està relacionada amb la memòria i els processos cognitius. Per aquesta raó, els inhibidors de la POP són compostos d’interès terapèutic per al tractament dels dèficits cognitius. Recentment, s’ha descobert que els inhibidors de la POP poden prevenir la patogènesis de la malaltia de Pàrkinson, probablement a través d’una interacció directa entre la POP i l’a-sinucleïna (la principal proteïna causant dels processos neurodegeneratius de la malaltia de Parkinson). Tot i que l’estructura cristal·logràfica de la POP està ben definida, no es sap quines són les transicions conformacionals que permeten completar el cicle catalític de la POP. Probablement, aquesta riquesa conformacional també té un paper rellevant en el control de les IPP. Malauradament, l’estudi conformacional complet de la POP és tot un repte degut al seu elevat pes molecular. En aquesta tesis doctoral s’ha emprat una combinació de tècniques biofísiques avançades (en concret, la resonància magnètica nuclear, la dispersió de raigs X de baix angle, i l’espectrometria de masses de mobilitat iònica) conjuntament amb simulacions de dinàmica molecular, per tal d’analitzar la dinàmica conformacional de la POP en solució. A més, s’ha estudiat la possible interacció entre la POP i l’a-sinucleïna mitjançant experiments de RMN. Els resultats obtinguts en aquesta tesi doctoral han demostrat que la POP es troba en solució en un equilibri conformacional lent entre conformacions obertes i tancades, originades a partir de la separació entre dos dominis. Els inhibidors de la POP causen una gran estabilització de la conformació tancada, amb la qual cosa l’equilibri dinàmic es desplaça totalment cap a aquesta conformació. A més, es va poder detectar una interacció dèbil i transitòria entre la POP i l’a-sinucleïna, que esdevenia especialment afavorida en la presència d’inhibidors. Així, els nostres resultats suggereixen que la diversitat conformacional de la POP es necessària per a la seva funció, i que els inhibidors poden desencadenar la seva funció biològica desplaçant l’equilibri conformacional.
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Link, Justin J. "Ultrafast Protein Conformation Dynamics." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1230584570.
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Hirtreiter, Angela Maria. "Protein Folding in Archaea." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-71656.
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Chavez, Leslie Lou. "Topology and protein folding /." Diss., Connect to a 24 p. preview or request complete full text in PDF formate. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3208633.
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Vasilkoski, Zlatko. "Protein folding computational studies /." Thesis, Connect to Dissertations & Theses @ Tufts University, 2003.
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Thesis (Ph.D.)--Tufts University, 2003.Adviser: David L. Weaver. Submitted to the Dept. of Physics. Includes bibliographical references. Access restricted to members of the Tufts University community. Also available via the World Wide Web;
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Saunders, Rhodri. "Co-translational protein folding." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526508.
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Pugh, Sara Dorothy. "Single molecule protein folding." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441320.
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Yoon, Hyun-suk. "Optimization Approaches to Protein Folding." Diss., Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/13937.
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This research shows optimization approaches to protein folding. The protein folding problem is to predict the compact three dimensional structure of a protein based on its amino acid sequence. This research focuses on ab-initio mathematical models to find provably optimal solutions to the 2D HP-lattice protein folding model.
We built two integer programming (IP) models and five constraint programming (CP) models. All the models give provably optimal solutions. We also developed some CP techniques to solve the problem
faster and then compared their computational times. We tested the models with several protein instances. My models, while they are probably too slow to use in practice, are significantly faster than the alternatives, and thus are mathematically relevant. We also provided reasons why protein folding is hard using complexity analysis.
This research will contribute to showing whether CP can be an alternative to or a complement of IP in the future. Moreover, figuring out techniques combining CP and IP is a prominent research issue and our work will contribute to that literature. It also shows which IP/CP strategies can speed up the running time for this type of problem. Finally, it shows why a mathematical approach to protein folding is especially hard not only mathematically, i.e. NP-hard, but also practically.
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Seibert, Mark Marvin. "Protein Folding and DNA Origami." Doctoral thesis, Uppsala universitet, Molekylär biofysik, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-121549.
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In this thesis, the folding process of the de novo designed polypeptide chignolin was elucidated through atomic-scale Molecular Dynamics (MD) computer simulations. In a series of long timescale and replica exchange MD simulations, chignolin’s folding and unfolding was observed numerous times and the native state was identified from the computed Gibbs free-energy landscape. The rate of the self-assembly process was predicted from the replica exchange data through a novel algorithm and the structural fluctuations of an enzyme, lysozyme, were analyzed. DNA’s structural flexibility was investigated through experimental structure determination methods in the liquid and gas phase. DNA nanostructures could be maintained in a flat geometry when attached to an electrostatically charged, atomically flat surface and imaged in solution with an Atomic Force Microscope. Free in solution under otherwise identical conditions, the origami exhibited substantial compaction, as revealed by small angle X-ray scattering. This condensation was even more extensive in the gas phase. Protein folding is highly reproducible. It can rapidly lead to a stable state, which undergoes moderate fluctuations, at least for small structures. DNA maintains extensive structural flexibility, even when folded into large DNA origami. One may reflect upon the functional roles of proteins and DNA as a consequence of their atomic-level structural flexibility. DNA, biology’s information carrier, is very flexible and malleable, adopting to ever new conformations. Proteins, nature’s machines, faithfully adopt highly reproducible shapes to perform life’s functions robotically.
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Itoh, Kazuhito, and Masaki Sasai. "Multidimensional theory of protein folding." American Institite of Physics, 2009. http://hdl.handle.net/2237/12626.
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Williams, Haydn Wyn. "Computer simulations of protein folding." Thesis, University of Nottingham, 2011. http://eprints.nottingham.ac.uk/12180/.
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Computer simulations of biological systems provide novel data while both supporting and challenging traditional experimental methods. However, continued innovation is required to ensure that these technologies are able to work with increasingly complex systems. Coarse–grained approximations of protein structure have been studied using a lattice model designed to find low–energy conformations. A hydrogen–bonding term has been introduced. The ability to form β–sheet has been demonstrated, and the intricacies of reproducing the more complex α–helix on a lattice have been considered. An alternative strategy, that of better utilising computing power through the technique of milestoning, has shown good agreement with previous experimental and computational work. The increased efficiency allows significantly less extreme simulation conditions to be applied than those used in alternative simulation methods, and allows more simulation repeats. Finally, the principles of Least Action Dynamics have been employed to combine the two approaches described above. By splitting a simulation trajectory into a number of smaller components, and using the lattice model to optimise the path from a start structure to an end structure, it has been possible to efficiently generate dynamical information using an alternative method to traditional molecular dynamics.
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Chintapalli, Sree Vamsee. "Closed loops in protein folding." Thesis, University of Essex, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494193.
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Danks, Gemma B. "Protein folding with L-systems." Thesis, University of York, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495868.
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