Biochemistry, Biophysics, and Structural Biology Commons^™

Developing An Application For Evolutionary Search For Computational Models Of Cellular Development, Nicolas Scott Cornia

Boise State University Theses and Dissertations

VPEvolve is a free and open source application that utilizes a Visual Programming Environment (VPE) for the setup of the Genetic Algorithm (GA), for optimization of computational models. Specifically, the User Interface uses connected glyphs to represent the genetic operators of mutation, reproduction, fitness and selection. These glyphs give the user an intuitive way to set the parameters for the GA, and better visualization of the population's flow through these operators.

VPEvolve is currently being developed alongside research being done in Biocomputing to create models of cellular regeneration based on the regenerative properties of Planaria or flatworms. Since these models …

Conservation Of Lipid Storage Droplet Proteins In Evolution Of Animalia, Jacob D. Bowman

Undergraduate Honors Thesis Projects

Lipolysis is a conserved pathway used by organisms for the mobilization of fatty acid (FA) out of triacylglycerol (TAG). Neutral lipids are stored in lipid-storage droplets (LSD) which are in nearly every cell of an organism. LSDs are the location of lipolysis. Perilipin proteins are lipid-droplet associated proteins. Perilipins interact with other proteins such as ATGL that breaks down TAG into FA and DAG. Because of its conservation as a whole system, this suggests that proteins of the same pathway are evolving together. This present study traces the evolutionary history of lipolysis-related proteins amongst individual organisms and classes of organisms …

Evaluation Of The Signature Molecular Descriptor With Blosum62 And An All-Atom Description For Use In Sequence Alignment Of Proteins, Lindsay M. Aichinger

Williams Honors College, Honors Research Projects

This Honors Project focused on a few aspects of this topic. The second is comparing the molecular signature kernels to three of the BLOSUM matrices (30, 62, and 90) to test the accuracy of the mathematical model. The kernel matrix was manipulated in order to improve the relationship by focusing on side groups and also by changing how the structure was represented in the matrix by increasing the initial height distance from the central atom (Height 1 and Height 2 included).

There were multiple design constraints for this project. The first was the comparison with the BLOSUM matrices (30, 62, …

Bioinformatic Solutions To Complex Problems In Mass Spectrometry Based Analysis Of Biomolecules, Ryan M. Taylor

Theses and Dissertations

Biological research has benefitted greatly from the advent of omic methods. For many biomolecules, mass spectrometry (MS) methods are most widely employed due to the sensitivity which allows low quantities of sample and the speed which allows analysis of complex samples. Improvements in instrument and sample preparation techniques create opportunities for large scale experimentation. The complexity and volume of data produced by modern MS-omic instrumentation challenges biological interpretation, while the complexity of the instrumentation, sample noise, and complexity of data analysis present difficulties in maintaining and ensuring data quality, validity, and relevance. We present a corpus of tools which improves …

Numerical Assessment Of Sequence Conservation In Flu-Virus Hemagglutinin, Scott S. Norton

Honors Scholar Theses

The flu virus was investigated to find a common recognition domain to which an antibody against human-infected viruses can bind. If such a target site is structurally and electrostaticly conserved or invariant, only a single antibody would be required to attack the virus in all cases. The sequence of one of the viral surface proteins contains 24 amino acids that do not vary through mutation. However, these amino acids are neither contiguous in sequence or in space, and the ones that are associated with each other are not readily accessible to an antibody. They do provide a first impression of …

Integrating Phage Therapy Into Western Medicine, Jacob B. Jaminet

Undergraduate Research Posters

The World Health Organization has described the rise of antibiotic use as a “global heath security emergency” (who.int). With the growing concern about antibiotic resistant bacteria, there has been an increased interest in bacteriophages. Bacteriophages are high-specific viruses that only infect bacteria. The use of bacteriophages medicinally to treat bacteria is called phage therapy. Research in phage therapy gained momentum until the introduction of antibiotics. While the USA and other Western countries accepted antibiotics, the Soviet Union and their satellite nations still continued to research phages. Since the funding for research was supplied by the Soviet military, the results of …

Genome-Wide Profiling Unveils Criticial Functions Of P53 In Human Embryonic Stem Cells, Kadir C. Akdemir

Dissertations and Theses (Open Access)

Embryonic stem cells (ESCs) possess two unique characteristics: infinite self-renewal and the potential to differentiate into almost every cell type (pluripotency). Recently, global expression analyses of metastatic breast and lung cancers revealed an ESC-like expression program or signature, specifically for cancers that are mutant for p53 function. Surprisingly, although p53 is widely recognized as the guardian of the genome, due to its roles in cell cycle checkpoints, programmed cell death or senescence, relatively little is known about p53 functions in normal cells, especially in ESCs. My hypothesis is that p53 has specific transcription regulatory functions in human ESCs (hESCs) that …

A Novel Algorithm For Validating Peptide Identification From A Shotgun Proteomics Search Engine, Ling Jian, Xinnan Niu, Zhonghang Xia, Parimal Samir, Chiranthani Sumanasekera, Zheng Mu, Jennifer L. Jennings, Kristen L. Hoek, Tara Allos, Leigh M. Howard, Kathryn M. Edwards, P. Anthony Weil, Andrew J. Link

Chemistry Faculty Research

Liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) has revolutionized the proteomics analysis of complexes, cells, and tissues. In a typical proteomic analysis, the tandem mass spectra from a LC–MS/MS experiment are assigned to a peptide by a search engine that compares the experimental MS/MS peptide data to theoretical peptide sequences in a protein database. The peptide spectra matches are then used to infer a list of identified proteins in the original sample. However, the search engines often fail to distinguish between correct and incorrect peptides assignments. In this study, we designed and implemented a novel algorithm called De-Noise to …

Utilizing Nmr Spectroscopy And Molecular Docking As Tools For The Structural Determination And Functional Annotation Of Proteins, Jaime Stark

Department of Chemistry: Dissertations, Theses, and Student Research

With the completion of the Human Genome Project in 2001 and the subsequent explosion of organisms with sequenced genomes, we are now aware of nearly 28 million proteins. Determining the role of each of these proteins is essential to our understanding of biology and the development of medical advances. Unfortunately, the experimental approaches to determine protein function are too slow to investigate every protein. Bioinformatics approaches, such as sequence and structure homology, have helped to annotate the functions of many similar proteins. However, despite these computational approaches, approximately 40% of proteins still have no known function. Alleviating this deficit will …

Computational Approaches To Anti-Toxin Therapies And Biomarker Identification, Rebecca Jane Swett

Wayne State University Dissertations

This work describes the fundamental study of two bacterial toxins with computational methods, the rational design of a potent inhibitor using molecular dynamics, as well as the development of two bioinformatic methods for mining genomic data.

Clostridium difficile is an opportunistic bacillus which produces two large glucosylating toxins. These toxins, TcdA and TcdB cause severe intestinal damage. As Clostridium difficile harbors considerable antibiotic resistance, one treatment strategy is to prevent the tissue damage that the toxins cause. The catalytic glucosyltransferase domain of TcdA and TcdB was studied using molecular dynamics in the presence of both a protein-protein binding partner and …

Disulfide By Design 2.0: A Web-Based Tool For Disulfide Engineering In Proteins, Douglas B. Craig, Alan A. Dombkowski

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Disulfide engineering is an important biotechnological tool that has advanced a wide range of research. The introduction of novel disulfide bonds into proteins has been used extensively to improve protein stability, modify functional characteristics, and to assist in the study of protein dynamics. Successful use of this technology is greatly enhanced by software that can predict pairs of residues that will likely form a disulfide bond if mutated to cysteines.

Results

We had previously developed and distributed software for this purpose: Disulfide by Design (DbD). The original DbD program has been widely used; however, it has a number …

Classification Of Multi-Domain Glycoside Hydrolases To Aid In The Enzymatic Production Of Biofuels From Biomass, Emi Leonard, Gregg Beckham, Deanne Sammond, Michael Crowley

STAR Program Research Presentations

Biomass conversion to renewable biofuels provides an alternative to conventional fossil-fuel based transportation fuels and a means to reduce dependence on foreign oil. However, plant cell walls have evolved to be quite resistant to enzymatic deconstruction, a phenomenon generally termed biomass recalcitrance. As enzymes represent a substantial cost in biofuels production, there is significant impetus to understand and improve their efficiency in converting cell wall carbohydrates to fermentable sugars. Much research has been conducted on single "free" enzymes with one catalytic unit per protein and on the much larger, complexed "cellulosomes" with many tens of catalytic units per protein, but …

Signals Delivered By Interleukin-7 Regulate The Activities Of Bim And Jund In T Lymphocytes, Shannon Moore Ruppert

Electronic Theses and Dissertations

Interleukin-7 (IL-7) is an essential cytokine for lymphocyte growth that has the potential for promoting proliferation and survival. While the survival and proliferative functions of IL-7 are well established, the identities of IL-7 signaling components in pathways other than JAK/STAT, that accomplish these tasks remain poorly defined. To this end, we used IL-7 dependent T-cells to examine those components necessary for cell growth and survival. Our studies revealed two novel signal transducers of the IL-7 growth signal: BimL and JunD. IL-7 promoted the activity of JNK (Jun N-terminal Kinase), and that JNK, in turn, drove the expression of JunD, a …

Hivtoolbox, An Integrated Web Application For Investigating Hiv, David P. Sargeant, Sandeep Deverasetty, Yang Luo, Angel Villahoz Baleta, Stephanie Zobrist, Viraj Rathnayake, Jacqueline C. Russo, Jay Vyas, Mark A. Muesing, Martin Schiller

Life Sciences Faculty Research

Many bioinformatic databases and applications focus on a limited domain of knowledge federating links to information in other databases. This segregated data structure likely limits our ability to investigate and understand complex biological systems. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and allows virologists and structural biologists to access sequence, structure, and functional relationships in an intuitive web application. HIV-1 integrase protein was used as a case study to show the utility of this application. We show how data integration facilitates identification of new questions and hypotheses much more rapid …

Practical Approach To Bioinformatics, Nigel Yarlett, Melissa Grigione

Cornerstone 3 Reports : Interdisciplinary Informatics

No abstract provided.

A Proposed Syntax For Minimotif Semantics, Version 1., Jay Vyas, Ronald J. Nowling, Mark W. Maciejewski, Sanguthevar Rajasekaran, Michael R. Gryk, Martin R. Schiller

Life Sciences Faculty Research

BACKGROUND:

One of the most important developments in bioinformatics over the past few decades has been the observation that short linear peptide sequences (minimotifs) mediate many classes of cellular functions such as protein-protein interactions, molecular trafficking and post-translational modifications. As both the creators and curators of a database which catalogues minimotifs, Minimotif Miner, the authors have a unique perspective on the commonalities of the many functional roles of minimotifs. There is an obvious usefulness in standardizing functional annotations both in allowing for the facile exchange of data between various bioinformatics resources, as well as the internal clustering of sets of …

Identification Of Trace Element-Containing Proteins In Genomic Databases, Vadim N. Gladyshev, Gregory V. Kryukov, Dmitri E. Fomenko, Dolph L. Hatfield

Vadim Gladyshev Publications

Development of bioinformatics tools provided researchers with the ability to identify full sets of trace element–containing proteins in organisms for which complete genomic sequences are available. Recently, independent bioinformatics methods were used to identify all, or almost all, genes encoding selenocysteine-containing proteins in human, mouse, and Drosophila genomes, characterizing entire selenoproteomes in these organisms. It also should be possible to search for entire sets of other trace element–associated proteins, such as metal-containing proteins, although methods for their identification are still in development.