Bioinformatics Commons^™

Elastin-Like Polypeptide As A Model To Study Intrinsically Disordered Proteins, Sadegh Majdi

Theses and Dissertations

The elastin-like polypeptide (ELP) is a well-studied structural protein that is easily amenable to amino acid (AA) sequence modifications and has the potential to yield a wide variety of uses in bioengineering and biomedical applications. One unique property of ELP is the inclusion of intrinsically disordered domains (IDP) within the structure that allow for its diversity of physical properties. While it is generally understood that amino acid sequence dictates protein folding arrangements, the contributions of specific amino acid sequences to the intrinsic disorder of ELP has yet to be fully resolved. Therefore, identifying the contributions of specific amino acid sequences …

Dynamics Of Redox-Driven Molecular Processes In Local And Systemic Plant Immunity, Philip Berg

Theses and Dissertations

The work here presents two main parts. In the first part, chapters 1 – 3 focus on dynamical systems modeling in plant immunity, whereas chapters 4 – 6 describe contributions to computational modeling and analysis of proteomics and genomics data. Chapter 1 investigates dynamical and biochemical patterns of reversibly oxidized cysteines (RevOxCys) during effector-triggered immunity (ETI) in Arabidopsis, examines the regulatory patterns associated with Arabidopsis thimet oligopeptidase 1 and 2’s (TOP1 and TOP2), roles in the RevOxCys events during ETI, and analyzes the redox phenotype of the top1top2 mutant. The second chapter investigates the peptidome dynamics during ETI …

Structure-Based Drug Discovery And Development Of Protein Structure Prediction Tools Using An Empirical Force Field, Noah B. Herrington

Theses and Dissertations

Traditional drug discovery has rapidly accelerated thanks to development of computational molecular modeling. The crucial component that these computational studies hinge upon is having a well-defined, and energetically favorable structure. Structures of proteins and ligands that meet these criteria are important for accurately simulating models used to study drug binding. To demonstrate the role of accurate structure simulation in the study of these events, this thesis presents, first, a story examining the problem of accurate structure modeling of ionizable residues within protein structures, specifically aspartic acid, glutamic acid, and histidine. I present our method, which uses the HINT force field …

Protein Structure And Interaction: The Role Of Aromatic Residues In Protein Structure And Interactions Between Pyridoxine 5'-Phosphate Oxidase/Dopa Decarboxylase, Mohammed H. Al Mughram

Theses and Dissertations

Naturally developed proteins are capable of carrying out a wide variety of molecular functions due to their highly precise three-dimensional structures, which are determined by their genetically encoded sequences of amino acids. A thorough knowledge of protein structures and interactions at the atomic level will enable researchers to get a deep foundational understanding of the molecular interactions and enzymatic processes required for cells, resulting in more effective therapeutic interventions. This dissertation intends to use structural knowledge from solved protein structures for two distinct objectives.

In the first project, we conducted a bioinformatics structural analysis of experimental protein structures using our …

Insights Into Halophilic Microbial Adaptation: Analysis Of Integrons And Associated Genomic Structures And Characterization Of A Nitrilase In Hypersaline Environments, Sarah Sonbol

Theses and Dissertations

Hypersaline environments are extreme habitats that can be exploited as biotechnological resources. Here, we characterized a nitrilase (NitraS-ATII) isolated from Atlantis II Deep brine pool. It showed higher thermal stability and heavy metal tolerance compared to a closely related nitrilase.

We also studied integrons in halophiles and hypersaline environments. Integrons are genetic platforms in which an integron integrase (IntI) mediates the excision and integration of gene cassettes at specific recombination sites. In order to search for integrons in halophiles and hypersaline metagenomes, we used a PCR-based approach, in addition to different bioinformatics tools, mainly IntegronFinder.

We found that integrons and …

Computational Analysis And Prediction Of Intrinsic Disorder And Intrinsic Disorder Functions In Proteins, Akila I. Katuwawala

Theses and Dissertations

COMPUTATIONAL ANALYSIS AND PREDICTION OF INTRINSIC DISORDER AND INTRINSIC DISORDER FUNCTIONS IN PROTEINS

By Akila Imesha Katuwawala

A dissertation submitted in partial fulfillment of the requirements for the degree of Engineering, Doctor of Philosophy with a concentration in Computer Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2021

Director: Lukasz Kurgan, Professor, Department of Computer Science

Proteins, as a fundamental class of biomolecules, have been studied from various perspectives over the past two centuries. The traditional notion is that proteins require fixed and stable three-dimensional structures to carry out biological functions. However, there is mounting evidence regarding a “special” class …

Understanding The Molecular And Cellular Functions Of Odd-Skipped Related 1 In Outflow Tract Development, Menglan Xiang

Theses and Dissertations

The cardiac outflow tract (OFT) is a transient conduit that connects the embryonic heart chambers to the vascular network. Transcription factor Osr1 promotes the proliferation and cell cycle progression of second heart field (SHF), an essential cell population that contribute to the developing OFT. In this study, we investigated the role of Osr1 in OFT development on cellular and molecular levels using a systems biology approach. We observed OFT rotation and elongation defects, as well as double-outlet right ventricle and overriding aorta as a result of SHF-specific deletion of Osr1. Using genetic inducible fate mapping, we showed that Osr1-expressing SHF …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

A Pipeline For Creation Of Genome-Scale Metabolic Reconstructions, Shaun W. Norris

Theses and Dissertations

The decreasing costs of next generation sequencing technologies and the increasing speeds at which they work have lead to an abundance of 'omic datasets. The need for tools and methods to analyze, annotate, and model these datasets to better understand biological systems is growing. Here we present a novel software pipeline to reconstruct the metabolic model of an organism in silico starting from its genome sequence and a novel compilation of biological databases to better serve the generation of metabolic models. We validate these methods using five Gardnerella vaginalis strains and compare the gene annotation results to NCBI and the …

G-Quadruplex Dna Structures And Site Specific Genetic Instability, Jonathan David Williams

Theses and Dissertations

Repetitive DNA comprises a majority of the human genome yet functions and overall impacts on site-specific genetic instability are not fully defined. Repetitive G-rich sequences have the propensity to form G-quadruplex (G4), which are stable non-B form DNA structures. G4 structures are conspicuously found at regions of site-specific instability. Even so, human genomic loci capable of forming this structure and their connection to DNA rearrangements are just beginning to be elucidated. My dissertation focuses on G4 structures and their capacity to promote site-specific changes in the human genome, particularly at oncogenes. I identified and investigated new biologically relevant G4 loci …

Dysregulation Of Micrornas In Blood As Biomarkers For Diagnosing Prostate Cancer, Rhonda W. Daniel

Theses and Dissertations

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers.

Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such …

Mysteries Of The Trypanosomatid Maxicircles: Characterization Of The Maxicircle Genomes And The Evolution Of Rna Editing In The Order Kinetoplastida, Preethi Ranganathan Iyengar

Theses and Dissertations

The trypanosomatid protists belonging to Order Kinetoplastida are some of the most successful parasites ever known to mankind. Their extreme physiological diversity and adaptability to different environmental conditions and host systems make them some of the most widespread parasites, causing deadly diseases in humans and other vertebrates.

This project focuses on their unique mitochondrion, called the kinetoplast, and more specifically involves the characterization of a part of their mitochondrial DNA (also called kinetoplast DNA or kDNA), the maxicircles, which are functional homologs of eukaryotic mitochondrial DNA in the kinetoplastid protists. We have sequenced and characterized the maxicircle genomes of 20 …