Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 12 of 12
Full-Text Articles in Chemistry
Turning Density Functional Theory Calculations Into Molecular Mechanics Simulations : Establishing The Fluctuating Density Model For Rna Nucleobases, Christopher A. Myers
Turning Density Functional Theory Calculations Into Molecular Mechanics Simulations : Establishing The Fluctuating Density Model For Rna Nucleobases, Christopher A. Myers
Legacy Theses & Dissertations (2009 - 2024)
Molecular mechanics (MD) simulations and density functional theory (DFT) have been the backbone of computational chemistry for decades. Due to its accuracy and computational feasibility, DFT has become the go-to method for theoretically predicting interaction energies, polarizability, and other electronic properties of small molecules at the quantum mechanical level. Although less fundamental than DFT, molecular mechanics (MM) algorithms have been just as influential in the fields of biology and chemistry, owing their success to the ability to compute measurable, macroscopic quantities for systems with tens of thousands to hundreds of thousands of atoms at a time. Nevertheless, MD simulations would …
Fluorescent Labelling Of Ribosomal Rna In Live Mammalian Cells, Amir Agharezaee
Fluorescent Labelling Of Ribosomal Rna In Live Mammalian Cells, Amir Agharezaee
Legacy Theses & Dissertations (2009 - 2024)
This thesis describes a bio-orthogonal chemistry-based approach for new methods of fluorescence labelling of RNA in live HeLa cells via an IEDDA reaction of TCO with tetrazine. The key step of the approach is synthesis of two nucleobase analogues which were modified with TCO and a masked 5′-phosphate group using aryl phosphonamidite chemistry. Synthesis of tubercidin and uridine analogues were considered in this investigation for incorporation into RNA in live HeLa cells. Synthetic approach was successful at installing the handle containing TCO to tubercidin and uridine to make compounds 12 and 21 respectively (the synthesis of both of which are …
Development Of Dual Functional Dna/Rna Nanostructures For Drug Delivery, Vibhav Amit Valsangkar
Development Of Dual Functional Dna/Rna Nanostructures For Drug Delivery, Vibhav Amit Valsangkar
Legacy Theses & Dissertations (2009 - 2024)
In addition to the traditional biochemical functions, DNA and RNA have been increasingly studied as building blocks for the formation of various 2D and 3D nanostructures. DNA has emerged as a versatile building block for programmable self-assembly. DNA-based nanostructures have been widely applied in biosensing, bioimaging, drug delivery, molecular computation and macromolecular scaffolding. A variety of strategies have been developed to functionalize these nanostructures. The major advantage is that DNA is a very stable molecule and its base-pairing properties can be easily utilized to control and program the formation of desired nanostructures. In addition, some of these DNA/RNA nanostructures have …
Exploration Of Nucleic Acid Hydrogran Bonding Using Molecular Mechanics And Dft Calculations, Simi Kaur
Exploration Of Nucleic Acid Hydrogran Bonding Using Molecular Mechanics And Dft Calculations, Simi Kaur
Biological Sciences
Many recent theoretical and experimental techniques have been developed to probe the structurefunction relationships of complex biomolecules. The roles of RNAs are dependent upon various intricate structural motifs and interactions, including hairpins, pseudoknots, long range territory contacts, bulges and internal loops, that are not easily captured by these methods. We had previously developed an enhanced replica exchange molecular dynamics method that incorporated secondary structure information in the form of distance restraints in order to effectively overcome kinetic barriers and sample conformational space. In several structures, restrained RNA base pairs near large bulges displayed a preference for stacking over hydrogen bonding …
Computational Modeling As A Tool For Designing Ligands And Receptors, Waqas S. Awan
Computational Modeling As A Tool For Designing Ligands And Receptors, Waqas S. Awan
Legacy Theses & Dissertations (2009 - 2024)
Computational methods can be used for a wide range of applications, especially regarding DNA and RNA. Interactions such as sugar torsions, receptor-ligand interactions, ligand docking/drug docking, receptor modeling, and drug design are excellent candidates for computational analysis and in silico experiments. The use of molecular dynamics software (GROMACS) coupled with molecular design software (MOE) produce insights that may have been otherwise difficult to assess. All these problems are academic in nature but have practical uses outside of academia. Understanding alternate linkages can lead to antibiotic assays to address potential superbug epidemics. Modeling DNA superstructures can provide insight into how large …
Technology Development For Detection Of Circulating Disease Biomarkers From Liquid Biopsies Using Multifunctional Nanomaterials, Mustafa Balcioglu
Technology Development For Detection Of Circulating Disease Biomarkers From Liquid Biopsies Using Multifunctional Nanomaterials, Mustafa Balcioglu
Legacy Theses & Dissertations (2009 - 2024)
Despite the advance health care, devastating health conditions such as cancer and infectious diseases that affect populations worldwide are too often not diagnosed until morbid symptoms become apparent in the late phase. Obtaining an early and accurate diagnosis that reveal a hidden lethal threat before the disease becomes complicated may dramatically reduce the severity of its impact on the patient’s life and increase the probability of survival. For example, in the case of ovarian cancer, which is the fifth most common malignancy and the fifth leading cause of cancer mortality in women in the US, the 5-year relative survival is …
Novel Nmr Based Technologies To Study Macromolecular Structures, Subhabrata Majumder
Novel Nmr Based Technologies To Study Macromolecular Structures, Subhabrata Majumder
Legacy Theses & Dissertations (2009 - 2024)
Nuclear Magnetic Resonance Spectroscopy (NMR) is one of the principle tools in structural biology to probe macromolecular structures and interactions. The atomic resolution afforded by this technique has been widely used to probe protein-protein, and protein-ligand interactions in-vitro. However, the natural milieu of the proteins is the living cell and the cellular cytoplasm is extremely heterogeneous. The NMR studies of folded protein in-cell, till now, have been limited by non-specific interactions of the cytosol. This thesis outlays a general methodology to study protein structure/interactions inside the living cells using NMR. In a closely related objective, it also describes the use …
Mass Spectrometry-Based Rnomics : Global Surveys Of Ribonucleotide Modifications As Possible Indicators Of Cell Identity, Epigenetic, Metabolic And Pathological State, Rebecca Erin Rose
Mass Spectrometry-Based Rnomics : Global Surveys Of Ribonucleotide Modifications As Possible Indicators Of Cell Identity, Epigenetic, Metabolic And Pathological State, Rebecca Erin Rose
Legacy Theses & Dissertations (2009 - 2024)
Discovery of the regulatory roles of non-protein coding RNAs (ncRNAs), once considered “junk” or “transcriptional noise”, has prompted a reassessment of the significance of the multifaceted activities of RNA in cellular response, which can result in cell transformation and diseased states. This reassessment, however, can only be accomplished if techniques are developed to capture, characterize and quantify the more than 100 covalent post-transcriptional modifications (PTMs) that adorn natural RNAs. Undoubtedly, the creation of high-throughput platforms such as next-generation sequencing and RNA-seq have provided unparalleled accuracy and sensitivity, however, they rely on strand amplification procedures that are blind to the known …
Molecular Dynamics Simulations Of Small Systems To Improve Base Pairing Parameters Of The Amber-99 Force Field, Angelo Christopher Setaro
Molecular Dynamics Simulations Of Small Systems To Improve Base Pairing Parameters Of The Amber-99 Force Field, Angelo Christopher Setaro
Legacy Theses & Dissertations (2009 - 2024)
Simulations of biochemical systems are being increasingly used to further our understanding of those systems. In broad strokes, chemical simulations can be broken into two categories, those that are rooted in a quantum mechanical approach and those that are classically rooted. Molecular dynamics is one such classical method, which propagates motion of a chemical system via repeatedly solving Newton’s Laws of motion. This approach is less computationally intensive than the quantum mechanical methods and allows for the simulation of systems of tens of thousands of atoms, if not more.
From Whole-Cell To Compartment- And Class-Specific Analysis Of Rna Post-Transcriptional Modifications, Ryan Quinn
From Whole-Cell To Compartment- And Class-Specific Analysis Of Rna Post-Transcriptional Modifications, Ryan Quinn
Legacy Theses & Dissertations (2009 - 2024)
The genomic structure of the human immunodeficiency virus type 1 (HIV-1) has proven difficult to examine by traditional high-resolution techniques. Structural probing and in silico modeling have been turned to the task instead. Computer models are only as robust as the data used to create them. A number of techniques were explored in this investigation to expand the utility of in silico modeling as it relates to HIV-1: the study of nucleoside modifications, and the probing of in vivo conformations of the 5'-untranslated region (5'-UTR) by cross-linking and affinity capture.
Ultraviolet Resonance Raman Spectroscopy For Characterization Of Rna Structure And Thermodynamics, Joseph Dustin Handen
Ultraviolet Resonance Raman Spectroscopy For Characterization Of Rna Structure And Thermodynamics, Joseph Dustin Handen
Legacy Theses & Dissertations (2009 - 2024)
Raman spectroscopy is a technique well suited for the study of biological molecules such as proteins, peptides, or RNAs. By utilizing an ultraviolet resonance Raman (UVRR) instrument, we are afforded a tremendous increase in sensitivity because of resonance enhancement. Additionally, this technique does not require any labeling. Moreover, this technique is better suited for studying biological systems than infrared absorption due to reduced interference from water. In this study, we apply techniques we have developed for the study of protein and peptide fibrillation to a model RNA homodimer. We demonstrate that UVRR spectroscopy is uniquely suited to monitoring the free …
Inhibition Of Glutamate Receptors By Constructing Bipartite Rna Aptamers, Jeffrey Hebert
Inhibition Of Glutamate Receptors By Constructing Bipartite Rna Aptamers, Jeffrey Hebert
Legacy Theses & Dissertations (2009 - 2024)
The relationship of excessive activity of AMPA-type glutamate receptors, and cell death, has long provided researchers a means of investigating neurodegenerative disorders, such as Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS). Inhibitors of AMPA receptor channels, including chemical and nucleic acid molecules such as RNA aptamers, have served as potential therapeutic agents and treatment of neurodegenerative disorders. In this study, building bipartite aptamers to enhance inhibitory potency, as compared with a monomeric aptamer of AMPA receptor, is described. An enhanced potency is due, at least in part; to the proximity effect in bipartite structures or binding of a monomeric …