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Probing The Regulatory Role Of Allostery Via Protein Dynamics Of Biological Systems, Michael G. Souffrant

Chemistry Dissertations

Allostery is a universal process in cellular interaction and function. Allosteric regulation occurs when local changes from a distant site of the biomolecular structure alter the changes at the binding site. Allosteric regulation is an intrinsic property, which is assumed to be a propagation of conformational or dynamical changes through a network of interactions from the regulatory site to the binding site cavity. Despite many approaches, the concept of allostery is vaguely understood, as this phenomenon occurs at different cellular levels for regulation. In this dissertation, we provide more insight on allosteric regulation, using three different protein systems as models …

Classification Of Nuclear Pastas Through Alpha Shapes Model, Daniela Ramirez Chavez

Open Access Theses & Dissertations

The nuclear pasta is important because is an astromaterial with incredible strength that may be a source for gravitational waves, which observe from the rotation of neutron stars. The characterization of the pasta is vital because the nuclear phases have transport properties - compressibility, neutrino opacity, thermal conductivity, and electrical conductivity - associated with their shape for which neutron stars may be sensitive. These properties could interpret observations of supernova neutrinos, magnetic field decay, and crust cooling of accreting neutron stars. Here, we study the nuclear pasta using alpha shapes to achieve a phase characterization with the Minkowski functionals (area, …

Multiscale Investigation Of Freeze Cast Process And Ion Transport For Graphene Aerogel Electrodes, Yu-Kai Weng

Doctoral Dissertations

Effective use of renewable energy resources has been regarded as the most promising solution to climate emergency and energy crisis. However, the fluctuating and intermittent nature of renewable resources causes stability issues in the electric grid. High-capacity electrical energy storage is essential to stabilize the electric power supply using renewable resources. Among various types of energy storage systems, organic redox flow battery (ORFB) has attracted attentions due to their high stability, flexibility, low cost, and environmental compatibility, but the performance of the ORFB still needs a significant improvement due to their low energy or current density. Specifically, even though the …

Comparative Analysis Of Conformational Transition Pathways In Homologous Proteins, Dylan Sebastien Ogden

Graduate Theses and Dissertations

Molecular dynamics (MD) simulations are routinely used to study the dynamics of proteins. However, conventional MD limited to the sampling of local conformational changes as the functionally important conformational transitions of proteins often extend beyond the timescales of the simulations employed, for example, membrane transport proteins. We have determined the combination of multiple MD based techniques that allows for a rigorous characterization of energetics and kinetics of large-scale conformational changes in membrane proteins. The methodology is based on biased, nonequilibrium collective variable based simulations including nonequilibrium pulling, string method with swarms of trajectories, bias-exchange umbrella sampling, and rate estimation techniques. …

A Numerical Simulation Of The Powder Bed Additive Manufacturing Process With Molecular Dynamics Simulation, Yeasir Mohammad Akib

Theses and Dissertations

Many manufacturing industries utilize powder bed fusion (PBF) since it can produce microscale precision 3D parts. During PBF, powder particles are selectively fused layer by layer using thermal energy. The build quality in the PBF process relies heavily on powder bed properties and thermal energy deposition. Powder flowability, spreadability, and packing fraction are some of the insightful factors that determine the quality of the powder bed. In this study, a two-dimensional powder bed is developed using the LAMMPS package. A cloud-based pouring of powders with varying volumes and initialization is adopted for the work. A blade-type and circular recoater is …

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 …

Molecular Dynamics Simulations Of The Adenylate Kinase Enzyme And Its Mutant States, Beata Izabella Dulko Smith

Chemistry & Biochemistry Dissertations

Adenylate kinase (AK) is a small, monomeric enzyme present across all domains of life. It is responsible for maintaining homeostasis of an intracellular adenylate pool and catalyzes a reversible transfer of the phosphoryl group from NTP (nucleoside triphosphate) to NMP producing two NDP molecules. While most known isoforms take ATP as phosphate donor, AK3 present in mitochondrial matrix employs GTP. Crystallographic investigations revealed that the basis for its selectivity for GTP over ATP came from an additional hydrogen bond between guanosine’s O6 and backbone nitrogen of threonine is responsible for recognition of GTP. Molecular dynamics (MD) simulations have demonstrated that …

Understanding Effect Of Ionic Liquid On Metalloproteins: Laccase And Azurin, Aashka Y. Patel

Theses and Dissertations

Interactions between ionic liquids and biomolecules have been of great interest due to the intrinsic properties of ionic liquids and the flexibility to mix and match cations and anions to create unique ionic liquids. A number of ionic liquid-biomolecule studies have focused on the interactions with proteins, including industrially relevant enzymes. One of these, laccase from Trametes versicolor, is a naturally derived enzyme used in the breakdown of phenolic compounds in a wide variety of industries, especially useful in breakdown of lignocellulosic materials. Here, a combination of experiments and molecular dynamics (MD) simulations were used to investigate the interactions …

Shear Localization In The Metallic Nanolayered Composites, Shujing Dong

Theses and Dissertations

In this dissertation, the influences of layer thickness (h), interface orientation relationship (OR) and dislocation slip activities on shear band (SB) formation mechanisms was investigated by means of molecular dynamics (MD) simulations.

The effect of h and dislocation slip systems on the shear localization in Cu-FCC/Nb-BCC MNCs was studied. The strain softening observed in those samples was triggered by the SB formation. The microstructure evolutions and dislocation slips revealed that the unsymmetrical dislocation transmission across the interface induces the shear localization and promotes the SB formation. The quantitative analysis of the change in the separation distance of initially …

Computational Methods, Investigations, And Codes To Support Corrosion Experiments In Molten Lead And Transfer To Reactor Conditions, Khaled A. Talaat

Nuclear Engineering ETDs

Lead cooled fast reactors have many potential economic advantages over other Generation IV reactor designs due to the high boiling point of lead (~1750 °C) at atmospheric pressure and excellent neutronic properties which have made them attractive to the commercial energy sector in the recent years. They, however, remain hampered by challenges in cladding material compatibility with the heavy liquid metal coolant. A forced circulation loop was established at the University of New Mexico (“Lobo Lead Loop”) to prequalify materials for Versatile Test Reactor (VTR) testing and to improve the understanding of flow accelerated corrosion in molten lead environment. Corrosion …

The Importance Of Fitting In: Investigating The Role Of Protein Dynamics In Dna Sequence Specificity, Kenneth Huang

Chemistry Dissertations

Specificity for protein/DNA complexes is well-studied in context of DNA sequence requirements, but the precise mechanisms for how segregation of affinity in consensus-bearing DNA has not been well characterized. Nonspecific sites are dictated by the lack of a consensus site, but high/low affinity binding rise from discrepancies in flanking sequences. Low-affinity DNA has been recently implicated as a general mechanism used by cells to regulate gene expression. Ets-1, the progenitor member of the ETS transcription family, offers a useful model to understand how cognate site discrimination occurs. We then performed molecular dynamics simulations of Ets-1 unbound and bound to nonspecific, …

Developing And Applying Computational Algorithms To Reveal Health-Related Biomolecular Interactions, Yixin Xie

Open Access Theses & Dissertations

Computational biology is an interdisciplinary area that applies computational approaches in biological big data, including protein amino acid sequences, genetic sequences, etc., which is widely used to analyze protein-protein interactions, make predictions in drug discovery, develop vaccines, etc. Popular methods include mathematical modeling, molecular dynamics simulations, data science mythology, etc. With the help of computational algorithms and applications, drug development is much faster than traditional processes, as it reduces risks early on in a drug discovery process and helps researchers select target candidates that have the highest potential for success. In my doctoral research, I applied multi-scale computational approaches to …

Spike Protein Structural Dynamics Of Sars-Cov-2 Coronaviruses Studied Using Molecular Dynamics, William Strickland

Biological Sciences Undergraduate Honors Theses

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has overwhelmingly impacted the global population, accounting for millions of confirmed infections and deaths over the last year. The virus’s influence on the health and safety of individuals, the economy, and daily life has been disruptive and devastating. While SARS-CoV-2 and SARS-CoV-1, two closely related members of the SARS coronaviruses, have shown the ability to cross the species barrier and infect humans, SARS-CoV-2 has predominantly been the virus responsible for the number of infections presently known. SARS-CoV-2 has also proven to be volatile, as many variants have …

Implications Of Metal Coordination In Damage And Recognition Of Nucleic Acids And Lipid Bilayers, Ana Dreab

Chemistry & Biochemistry Theses & Dissertations

Metal ions have a myriad of biological functions from structural stability to enzymatic (de)activation and metabolic electron transfer. Redox-active metals also mediate the formation of reactive oxygen species which may either cause oxidative damage or protect cellular components. Computational modeling is used here to investigate the role of (1) metal-ion binding to antimicrobial peptides, (2) metal-ion removal and disulfide formation on zinc finger (ZF) proteins, and (3) coordination of thiones/selones for the prevention of metal-mediated redox damage.

Piscidins, natural-occurring antimicrobial peptides, efficiently kill bacteria by targeting their membranes. Their efficacy is enhanced in vitro by metal-binding and the presence of …

Computational Studies On Polyunsaturated Fatty Acid Uptake And Its Effects On Antimicrobial Resistance, Andrew Turgeson

Masters Theses and Doctoral Dissertations

The topic of this research was initiated by the discovery, in part by Dr. David Giles, that Vibrio cholerae, the enteric bacteria responsible for the disease cholera, has the ability to uptake and utilize long chain polyunsaturated fatty acids up to 22 carbon atoms long. Before this discovery was made, conventional belief was that fatty acids of greater than 18 carbons long were toxic to bacteria. Further investigations have revealed that this uptake is not unique to Vibrio cholerae, and a range of bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and even Escherichia coli have been found to …

Defining Interactions Between Deformable Dna Origami And Lipid Bilayers Through Molecular Dynamics Simulation, Zachary A. Loyd

Chancellor’s Honors Program Projects

No abstract provided.

A Molecular Dynamics Study Of The Laser Sintering Process And Subsequent Mechanical Properties Of Γ-Tial Nanoparticles, Eleanor Dickens

Honors Theses

Using molecular dynamics (MD) simulations, the laser sintering additive manufacturing process is investigated through the observation of γ-TiAl nanoparticles. This process is conducted using both uni-directional chain and stacking configurations. By mimicking the heating process and varying laser sintering parameters such as heating rater, sintering temperature, and particle orientation, the fusion behavior and resulting products are analyzed for both chain and stacking NP patterns. In of single chain cases, it is noticed that slower heating rates and higher melting temperatures yield larger neck growth between each individual particle and thus produce a more stable product. This leads to stronger mechanical …

Functional Evolutionary Adaptation Of Binding Dynamics In The Sars-Cov-2/Ace2 Interface From Bats To Humans, Madhusudan Rajendran

Theses

The COVID-19 pandemic highlights the substantial public health, economic, and societal consequences of virus spillover from a wildlife reservoir. Widespread human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also presents a new set of challenges when considering viral spillover from people to naïve wildlife and other animal populations. Here, we used molecular dynamic (MD) simulations to understand the transmission of the SARS-CoV-2 virus from bats to humans and investigate the evolution of the various human variants. More specifically, we used MD simulations to understand the atomic fluctuation dampening at the receptor-binding domain (RBD)/ angiotensin-converting enzyme 2 (ACE2) interface …

Nonhematopoietic Erythropoietin: A Study Of Signaling, Structure, And Behavior, Nicholas John Pekas

Dissertations and Theses

Erythropoietin (EPO) is a cytokine hormone known for initiating red blood cell proliferation by binding to its homodimer receptor (EPOR)2 in the bone marrow. Recent progress in neurobiology has shown that EPO also exerts robust neurotrophic and neuroprotective activity in the CNS. It is widely thought that EPO’s neurotrophic activity is centrally involved in its antidepressant and cognitive enhancing effects. However, EPO’s potent erythropoietic effects prevent it from being used in the clinic to treat psychiatric disorders. A chemically engineered non-erythropoietic derivative of EPO, carbamoylated EPO (CEPO), produces psychoactive effects without activating hematopoiesis. However, CEPO is expensive to produce and …

Characterizing The Effects Of Solvent And Analyte Properties On Ionization Efficiency By Novel Field-Free And Field-Enabled Ionization Techniques, Kinkini Udara Jayasundara

Graduate Theses, Dissertations, and Problem Reports

In recent years the mass spectrometry (MS) area of field and/or direct analysis has grown dramatically. As a result, field-portable and miniaturized mass spectrometers, introduced only a few years ago, are proliferating. A highly desired feature for field-portable MS, or in-field analysis, is the ability to use ionization techniques requiring very little sample preparation as well as an ability to generate the ions under ambient conditions. Recently, a new ambient ionization technique termed vibrating sharp-edge spray ionization (VSSI) has been introduced which overcomes the field-portable limitations of other spray-based methods including the requirements for auxiliary components (e.g., nebulizing gas and …

Multilevel Computational Investigation Into The Dynamics And Reaction Mechanisms Of Non-Heme Iron And 2-Oxoglutarate Dependent Enzymes, Shobhit Sanjeev Chaturvedi

Dissertations, Master's Theses and Master's Reports

Computational chemistry methods have been extensively applied to investigate biological systems. This dissertation utilizes a multilevel computational approach to explore the dynamics and reaction mechanisms of two groups of enzymes belonging to non-heme Fe(II) and 2-oxoglutarate (2OG) dependent superfamily – histone lysine demethylases from class 7 and ethylene forming enzyme (EFE). Chapter 2 uncovers the role of conformational dynamics in the substrate selectivity of histone lysine demethylases 7A and 7B. The molecular dynamics (MD) simulations of the two enzymes revealed the importance of linker flexibility and dynamics in relative orientations of the reader (PHD) and the catalytic (JmjC) domains. Chapter …

Review Of Current Reactive Force Field Potentials For Use In Simulating The Atomic Layer Deposition Of Alumina On Aluminum, Devon T. Romine

MSU Graduate Theses

Alumina has recently garnered quite a bit of attention for use as a tunnel barrier in Josephson tunnel junctions. The quality of the metal oxide layer in the Josephson tunnel junction is a key factor in its effectiveness. To optimize the deposition method of alumina, we need a deep understanding of the large-scale surface interactions that cannot be reached using ab initio molecular dynamics. In this study, I have compared two existing reactive force field (ReaxFF) parameters to determine their abilities to model the atomic layer deposition (ALD) of alumina on an aluminum surface. ReaxFF molecular dynamics was chosen because …

Combinatorial Approaches For Effective Design, Synthesis, And Optimization Of Enzyme-Based Conjugates, Jordan Scott Chapman

Graduate Theses, Dissertations, and Problem Reports

The specificity and efficiency with which enzymes catalyze selective chemical reactions far exceeds the performance of traditional heterogeneous catalysts that are predominant in industrial applications such as conversion of commodity chemicals to value-added products, fuel cells, and petroleum refinement. Moreover, biocatalysts exhibit exceptionally high product turnover at ambient conditions with little health and environmental burden. These advantageous qualities have led to the prolific use of enzyme catalysis in pharmaceutical, detergents, and food preservation industries wherein their use has greatly reduced waste generation, Unfortunately, the full slate of benefits that enzymes can impart to a broader range of chemical processes is …

Molecular Modeling Of High-Performance Polymers, Sagar Umesh Patil

Dissertations, Master's Theses and Master's Reports

High-performance polymers are extensively used in the aerospace and aeronautics industries due to their low density, high specific strength, and high specific stiffness. These properties along with better infiltration with reinforcements [carbon nanotubes (CNTs), glass, etc.] capability make them an excellent candidate to fabricate Polymer Matrix Composites (PMCs) tailored for specific applications. The applications range from products used daily to deep space exploration. These materials are subjected to varying temperatures and pressures during fabrication and in service. Therefore, the evolution of their intrinsic properties needs to be studied and their ability to sustain extreme environmental conditions in outer space needs …