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Description
This thesis explores a wide array of topics related to the protein folding problem, ranging from the folding mechanism, ab initio structure prediction and protein design, to the mechanism of protein functional evolution, using multi-scale approaches. To investigate the role of native topology on folding mechanism, the native topology is dissected into non-local and local contacts. The number of non-local contacts and non-local contact orders are both negatively correlated with folding rates, suggesting that the non-local contacts dominate the barrier-crossing process. However, local contact orders show positive correlation with folding rates, indicating the role of a diffusive search in the denatured basin. Additionally, the folding rate distribution of E. coli and Yeast proteomes are predicted from native topology. The distribution is fitted well by a diffusion-drift population model and also directly compared with experimentally measured half life. The results indicate that proteome folding kinetics is limited by protein half life. The crucial role of local contacts in protein folding is further explored by the simulations of WW domains using Zipping and Assembly Method. The correct formation of N-terminal β-turn turns out important for the folding of WW domains. A classification model based on contact probabilities of five critical local contacts is constructed to predict the foldability of WW domains with 81% accuracy. By introducing mutations to stabilize those critical local contacts, a new protein design approach is developed to re-design the unfoldable WW domains and make them foldable. After folding, proteins exhibit inherent conformational dynamics to be functional. Using molecular dynamics simulations in conjunction with Perturbation Response Scanning, it is demonstrated that the divergence of functions can occur through the modification of conformational dynamics within existing fold for β-lactmases and GFP-like proteins: i) the modern TEM-1 lactamase shows a comparatively rigid active-site region, likely reflecting adaptation for efficient degradation of a specific substrate, while the resurrected ancient lactamases indicate enhanced active-site flexibility, which likely allows for the binding and subsequent degradation of different antibiotic molecules; ii) the chromophore and attached peptides of photocoversion-competent GFP-like protein exhibits higher flexibility than the photocoversion-incompetent one, consistent with the evolution of photocoversion capacity.
ContributorsZou, Taisong (Author) / Ozkan, Sefika B (Thesis advisor) / Thorpe, Michael F (Committee member) / Woodbury, Neal W (Committee member) / Vaiana, Sara M (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
Description
Proteins are a fundamental unit in biology. Although proteins have been extensively studied, there is still much to investigate. The mechanism by which proteins fold into their native state, how evolution shapes structural dynamics, and the dynamic mechanisms of many diseases are not well understood. In this thesis, protein folding is explored using a multi-scale modeling method including (i) geometric constraint based simulations that efficiently search for native like topologies and (ii) reservoir replica exchange molecular dynamics, which identify the low free energy structures and refines these structures toward the native conformation. A test set of eight proteins and three ancestral steroid receptor proteins are folded to 2.7Å all-atom RMSD from their experimental crystal structures. Protein evolution and disease associated mutations (DAMs) are most commonly studied by in silico multiple sequence alignment methods. Here, however, the structural dynamics are incorporated to give insight into the evolution of three ancestral proteins and the mechanism of several diseases in human ferritin protein. The differences in conformational dynamics of these evolutionary related, functionally diverged ancestral steroid receptor proteins are investigated by obtaining the most collective motion through essential dynamics. Strikingly, this analysis shows that evolutionary diverged proteins of the same family do not share the same dynamic subspace. Rather, those sharing the same function are simultaneously clustered together and distant from those functionally diverged homologs. This dynamics analysis also identifies 77% of mutations (functional and permissive) necessary to evolve new function. In silico methods for prediction of DAMs rely on differences in evolution rate due to purifying selection and therefore the accuracy of DAM prediction decreases at fast and slow evolvable sites. Here, we investigate structural dynamics through computing the contribution of each residue to the biologically relevant fluctuations and from this define a metric: the dynamic stability index (DSI). Using DSI we study the mechanism for three diseases observed in the human ferritin protein. The T30I and R40G DAMs show a loss of dynamic stability at the C-terminus helix and nearby regulatory loop, agreeing with experimental results implicating the same regulatory loop as a cause in cataracts syndrome.
ContributorsGlembo, Tyler J (Author) / Ozkan, Sefika B (Thesis advisor) / Thorpe, Michael F (Committee member) / Ros, Robert (Committee member) / Kumar, Sudhir (Committee member) / Shumway, John (Committee member) / Arizona State University (Publisher)
Created2011
Description
Infections caused by the Hepatitis C Virus (HCV) are very common worldwide, affecting up to 3% of the population. Chronic infection of HCV may develop into liver cirrhosis and liver cancer which is among the top five of the most common cancers. Therefore, vaccines against HCV are under intense study in order to prevent HCV from harming people's health. The envelope protein 2 (E2) of HCV is thought to be a promising vaccine candidate because it can directly bind to a human cell receptor and plays a role in viral entry. However, the E2 protein production in cells is inefficient due to its complicated matured structure. Folding of E2 in the endoplasmic reticulum (ER) is often error-prone, resulting in production of aggregates and misfolded proteins. These incorrect forms of E2 are not functional because they are not able to bind to human cells and stimulate antibody response to inhibit this binding. This study is aimed to overcome the difficulties of HCV E2 production in plant system. Protein folding in the ER requires great assistance from molecular chaperones. Thus, in this study, two molecular chaperones in the ER, calreticulin and calnexin, were transiently overexpressed in plant leaves in order to facilitate E2 folding and production. Both of them showed benefits in increasing the yield of E2 and improving the quality of E2. In addition, poorly folded E2 accumulated in the ER may cause stress in the ER and trigger transcriptional activation of ER molecular chaperones. Therefore, a transcription factor involved in this pathway, named bZIP60, was also overexpressed in plant leaves, aiming at up-regulating a major family of molecular chaperones called BiP to assist protein folding. However, our results showed that BiP mRNA levels were not up-regulated by bZIP60, but they increased in response to E2 expression. The Western blot analysis also showed that overexpression of bZIP60 had a small effect on promoting E2 folding. Overall, this study suggested that increasing the level of specific ER molecular chaperones was an effective way to promote HCV E2 protein production and maturation.
ContributorsHong, Fan (Author) / Mason, Hugh (Thesis advisor) / Gaxiola, Roberto (Committee member) / Chang, Yung (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2011
Description
How do you convey what’s interesting and important to you as an artist in a digital world of constantly shifting attentions? For many young creatives, the answer is original characters, or OCs. An OC is a character that an artist creates for personal enjoyment, whether based on an already existing story or world, or completely from their own imagination.
As creations made for purely personal interests, OCs are an excellent elevator pitch to talk one creative to another, opening up opportunities for connection in a world where communication is at our fingertips but personal connection is increasingly harder to make. OCs encourage meaningful interaction by offering themselves as muses, avatars, and story pieces, and so much more, where artists can have their characters interact with other creatives through many different avenues such as art-making, table top games, or word of mouth.
In this thesis, I explore the worlds and aesthetics of many creators and their original characters through qualitative research and collaborative art-making. I begin with a short survey of my creative peers, asking general questions about their characters and thoughts on OCs, then move to sketching characters from various creators. I focus my research to a group of seven core creators and their characters, whom I interview and work closely with in order to create a series of seven final paintings of their original characters.
As creations made for purely personal interests, OCs are an excellent elevator pitch to talk one creative to another, opening up opportunities for connection in a world where communication is at our fingertips but personal connection is increasingly harder to make. OCs encourage meaningful interaction by offering themselves as muses, avatars, and story pieces, and so much more, where artists can have their characters interact with other creatives through many different avenues such as art-making, table top games, or word of mouth.
In this thesis, I explore the worlds and aesthetics of many creators and their original characters through qualitative research and collaborative art-making. I begin with a short survey of my creative peers, asking general questions about their characters and thoughts on OCs, then move to sketching characters from various creators. I focus my research to a group of seven core creators and their characters, whom I interview and work closely with in order to create a series of seven final paintings of their original characters.
ContributorsCote, Jacqueline (Author) / Button, Melissa M (Thesis director) / Dove-Viebahn, Aviva (Committee member) / School of Art (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
In the past ten years, the United States’ sound recording industries have experienced significant decreases in employment opportunities for aspiring audio engineers from economic imbalances in the music industry’s digital streaming era and reductions in government funding for career and technical education (CTE). The Recording Industry Association of America reports promises of music industry sustainability based on increasing annual revenues in paid streaming services and artists’ high creative demand. The rate of new audio engineer entries in the sound recording subsection of the music industry is not viable to support streaming artists’ high demand to engineer new music recordings. Offering CTE programs in secondary education is rare for aspiring engineers with insufficient accessibility to pursue a post-secondary or vocational education because of financial and academic limitations. These aspiring engineers seek alternatives for receiving an informal education in audio engineering on the Internet using video sharing services like YouTube to search for tutorials and improve their engineering skills. The shortage of accessible educational materials on the Internet restricts engineers from advancing their own audio engineering education, reducing opportunities to enter a desperate job market in need of independent, home studio-based engineers. Content creators on YouTube take advantage of this situation and commercialize their own video tutorial series for free and selling paid subscriptions to exclusive content. This is misleading for newer engineers because these tutorials omit important understandings of fundamental engineering concepts. Instead, content creators teach inflexible engineering methodologies that are mostly beneficial to their own way of thinking. Content creators do not often assess the incompatibility of teaching their own methodologies to potential entrants in a profession that demands critical thinking skills requiring applied fundamental audio engineering concepts and techniques. This project analyzes potential solutions to resolve the deficiencies in online audio engineering education and experiments with structuring simple, deliverable, accessible educational content and materials to new entries in audio engineering. Designing clear, easy to follow material to these new entries in audio engineering is essential for developing a strong understanding for the application of fundamental concepts in future engineers’ careers. Approaches to creating and designing educational content requires translating complex engineering concepts through simplified mediums that reduce limitations in learning for future audio engineers.
ContributorsBurns, Triston Connor (Author) / Tobias, Evan (Thesis director) / Libman, Jeff (Committee member) / Department of Information Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
There has been a recent push for queer fiction, especially in the young adult genre, whose focus is gay and lesbian relationships. This growth is much needed in terms of visibility and the furthering of acceptance, but there are still subjects within the LGBTQ+ community that need to be addressed, including bisexual, asexual, and non-binary erasure. There are many people who claim that these identities do not exist, are labels used as a stepping stone on one's journey to discovering that they are homosexual, or are invented excuses for overtly promiscuous or prudish behavior. The existence of negative stereotypes, particularly those of non-binary individuals, is largely due to a lack of visibility and respectful representation within media and popular culture. However, there is still a dearth of non-binary content in popular literature outside of young adult fiction. Can You See Me? aims to fill the gap in bisexual, asexual, and non-binary representation in adult literature. Each of the four stories that make up this collection deals with an aspect of gender and/or sexuality that has been erased, ignored, or denied visibility in American popular culture. The first story, "We'll Grow Lemon Trees," examines bisexual erasure through the lens of sociolinguistics. A bisexual Romanian woman emigrates to Los Angeles in 1989 and must navigate a new culture, learn new languages, and try to move on from her past life under a dictatorship where speaking up could mean imprisonment or death. The second story "Up, Down, All Around," is about a young genderqueer child and their parents dealing with microaggressions, examining gender norms, and exploring personal identity through imaginary scenarios, each involving an encounter with an unknown entity and a colander. The third story, "Aces High," follows two asexual characters from the day they're born to when they are 28 years old, as they find themselves in pop culture. The two endure identity crises, gender discrimination, erasure, individual obsessions, and prejudice as they learn to accept themselves and embrace who they are. In the fourth and final story, "Mile Marker 72," a gay Mexican man must hide in plain sight as he deals with the death of his partner and coming out to his best friend, whose brother is his partner's murderer.
ContributorsOchser, Jordyn M. (Author) / Bell, Matt (Thesis director) / Free, Melissa (Committee member) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Pandora is a play exploring our relationship with gendered technology through the lens of artificial intelligence. Can women be subjective under patriarchy? Do robots who look like women have subjectivity? Hoping to create a better version of ourselves, The Engineer must navigate the loss of her creation, and Pandora must navigate their new world. The original premiere run was March 27-28, 2018, original cast: Caitlin Andelora, Rikki Tremblay, and Michael Tristano Jr.
ContributorsToye, Abigail Elizabeth (Author) / Linde, Jennifer (Thesis director) / Abele, Kelsey (Committee member) / Department of Information Systems (Contributor) / Economics Program in CLAS (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
After freelancing on my own for the past year and a half, I have realized that one of the biggest obstacles to college entrepreneurs is a fear or apprehension to sales. As a computer science major trying to sell my services, I discovered very quickly that I had not been prepared for the difficulty of learning sales. Sales get a bad rap and very often is the last thing that young entrepreneurs want to try, but the reality is that sales is oxygen to a company and a required skill for an entrepreneur. Due to this, I compiled all of my knowledge into an e-book for young entrepreneurs starting out to learn how to open up a conversation with a prospect all the way to closing them on the phone. Instead of starting from scratch like I did, college entrepreneurs can learn the bare basics of selling their own services, even if they are terrified of sales and what it entails. In this e-book, there are tips that I have learned to deal with my anxiety about sales such as taking the pressure off of yourself and prioritizing listening more than pitching. Instead of trying to teach sales expecting people to be natural sales people, this e-book takes the approach of helping entrepreneurs that are terrified of sales and show them how they can cope with this fear and still close a client. In the future, I hope young entrepreneurs will have access to more resources that handle this fear and make it much easier for them to learn it by themselves. This e-book is the first step.
ContributorsMead, Kevin Tyler (Author) / Sebold, Brent (Thesis director) / Kruse, Gabriel (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
South Korea possesses the only culture to successfully create a transnationality and hybridity formula that is not replicable. So why Korea and why now? The goal of this thesis creative project is to demonstrate the marketing and communications strategies used in the arts and culture industry to drive global awareness and interest in K-Pop. In order to achieve that goal, I created HellotoHallyu.com, a website designed for an audience of Millennials and Generation Z English speakers to increase their awareness of the growth and impact of the Korean Wave in a fun and engaging way. So those who may hear a song by K-Pop idol group BTS on a music awards show in the U.S. can get themselves up-to-speed before diving into the fast-paced world of K-culture gossip sites and forums. Hello to Hallyu delivers consumer-friendly, educational content easily understood by English speakers with no prior knowledge of Korean culture, while still piquing the interest of K-pop connoisseurs. It provides the background necessary for even the most dedicated fans to glean new knowledge of Korea's cultural industry and a new perspective on the content they consume. Hello to Hallyu is based on a combination of secondary and primary research conducted over four semesters beginning Spring 2017 and continuing through Spring 2018. This project is set up as an ever-expanding resource freely available to anyone with internet access. The research required to maintain the site will continue with the Wave. However, the content currently on the site is evergreen, a documentation of the history of the Wave as explained in peer-reviewed articles and by Dr. Ingyu Oh as well as a documentation of my personal experience with Hallyu while in Korea and as a Westerner living in the U.S. The site's goal is to demonstrate the marketing and communications strategies used in the industry to drive global awareness and interest. Through this means, Hello to Hallyu aims to provide fully developed multimedia content intended to increase English speakers' awareness of the growth and impact of the Korean Wave as shown through site visits, content views, and audience engagement.
ContributorsTravis, Lisa Anne (Author) / Hass, Mark (Thesis director) / Shewell, Justin (Committee member) / Walter Cronkite School of Journalism and Mass Communication (Contributor) / School of Film, Dance and Theatre (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This honors thesis outlines a method for teaching argument writing in the secondary classroom, including the elements of an argument based upon the Toulmin method, and diverse ways to help students who are all types of learners become engaged and receive the support they need. It includes all elements of argument, including evidence, warrants, backing, counterargument, claims, theses, the rhetorical triangle and the rhetorical appeals, including definitions and how they fit together in an argumentative essay. The largest portion of the project is dedicated to activities and resources for teachers based upon all of those elements, along with activities for the writing process as a whole. These activities are based upon the student's individual experience as well as various scholarly resources from leading professionals in the curriculum development field for English Language Arts. This is not meant to be an end-all be-all solution for teaching argument writing, but rather one of many resources that teachers can use in their classroom. This 30-page paper, including references, are condensed into an accessible website for teachers to use more easily. Each tab on the website refers to a different element or focus of the argument writing process, with both a definition and introduction as well as one or more activities for teachers to implement into the classroom. The activities are versatile and general for the purpose of teachers being able to include them into whatever curriculum they are currently teaching. The goal is that they can add argument instruction into what they are already either willingly or being required to teach in an easy and logical way. The website is available for any secondary teachers to use as they see fit at www.teachingargumentwriting.weebly.com.
ContributorsBrooks, Jenna Nicole (Author) / Blasingame, James (Thesis director) / Barnett, Juliet (Committee member) / Division of Teacher Preparation (Contributor) / School of Film, Dance and Theatre (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05