Doctor of Philosophy, University of Akron, 2014, Polymer Science

For decades, device design has focused on decreasing length scales. In computer and electronic engineering, small feature sizes allow increasing computational power in ever-smaller packages; in medicine, nanoscale in vivo devices and sensors and coatings have myriad applications. These applications all focus strongly on material/component interfaces. While recent advances in experimental techniques probing interfaces at nanometer and sub-nanometer scales have improved dramatically, computational simulation remains vital to obtaining detailed information about structure and energetics in nanometer-scale interactions at interfaces and the physical properties arising from interactions at larger scales. We start with all-atom molecular dynamics simulations of methane and chloromethane adsorption on the (100) surface of molybdenum to understand adsorbate polarity/geometry and substrate interaction potential effects on interfacial structure, packing and energetics. For featureless substrates, adsorbate geometry and orientation do not influence packing and affinity. Substrates with explicit surface structure show cooperation between substrate and adsorbate geometry via adsorption-site preference. Methane prefers sites over unit cell faces, roughly commensurate with the Mo surface, whereas chloromethane invites disorder, orienting its long axis along ”bridges” between surface Mo atoms. In the second phase, we used a coarse-grained bead-spring model to perform simulations of bottle-brush homopolymers tethered to a wall substrate at long time/length scales. We studied the intra- and intermolecular accumulation of tension in tethered bottle-brush backbones vs. bottle-brush dimensions and surface grafting density. Variations in bond force and bottle-brush/component shape and size descriptors uncovered three tension ”regimes”: (i) an isolated-brush regime (low surface grafting density), where intramolecular interactions dominate and tension is minimal; (ii) a ”soft-contac (open full item for complete abstract)

Committee: Mesfin Tsige Dr. (Advisor); Mark Foster Dr. (Committee Member); Shi-Qing Wang Dr. (Committee Member); Gustavo Carri Dr. (Committee Member); Jutta Luettmer-Strathmann Dr. (Committee Member) Subjects: Condensed Matter Physics; Materials Science; Molecular Physics; Physical Chemistry; Physics; Polymers; Theoretical Physics

Doctor of Philosophy, University of Akron, 2020, Polymer Engineering

The nature of glassy aging has been a topic of study for over half a century, and yet a number of open questions remain in the understanding of the glassy state. Since a polymer's physical and mechanical properties are directly dependent on its molecular structure and changes in that structure alter the physical properties of the glass, considerable economic impact can result from aging-related physical changes. Characterization of aging dynamics in under-dense and over-dense glasses and a comparison of the aging response in solvent-processed vs thermally-quenched glasses are two important questions that are addressed here. This work reports on the development of a protocol for studying physical aging via molecular dynamics simulation after a near-instantaneous temperature quench. The resulting data display characteristic experimental signatures of glassy aging in both a pure polymer and a polymer-plasticizer system, indicating that this protocol can potentially be used to study aging in a variety of systems. Results indicate that aging dynamics in under-dense and over-dense glasses are fundamentally different in character. Unlike in under-dense glasses, translational dynamics in over-dense glasses are mechanistically different than relaxation in equilibrium glass-forming liquids, which is supported by the finding that relaxation in over-dense glasses occurs through an explosive burst of superdiffusive motion. Addition of a plasticizer appears to moderate this response compared to that of the pure polymer system, which can be attributed to a decrease in system fragility in the plasticized system. Higher additive loadings may have an even greater effect and further research would be beneficial in clarifying this. Aging relaxation time in over-dense glasses obeys a zero parameter dependence on purely equilibrium properties. This finding enables prediction of non-equilibrium relaxation time given knowledge only of the starting temperature and the in-equilibrium (open full item for complete abstract)

Committee: David Simmons (Advisor); Kevin Cavicchi (Committee Chair); Ruel McKenzie (Committee Member); Mark Foster (Committee Member); Jutta Luettmer-Strathmann (Committee Member) Subjects: Condensed Matter Physics; Engineering; Polymers

Doctor of Philosophy, University of Akron, 2015, Polymer Engineering

Bioengineered colloidal noble metal nanoparticles have received much attention thanks to their superior functionality in variety of applications including catalysis, nanoelectronics, biosensors, and biomedicine. Size, shape, and surface features dictate the functionality while the underlying mechanisms of interactions at the interface of biomolecules and nanoscale metal substrates are not yet fully understood. Here, we carried out extensive parallel molecular dynamics simulations to explain how soft epitaxy determines facet specificity of several mutant peptides (S7: SSFPQPN as base sequence) on various facets of Pt crystals. Binding differentials between facets strongly depend on the presence of phenyl rings, including “lie-flat” attractive configurations on the {111} surface that match the hexagonal pattern of epitaxial sites and repulsive “stand-up” configurations on the {100} surface. We uncovered the molecular mechanism of specific recognition of Pt nanocubes and the evolution of cubic shapes from cuboctahedral seed crystals by combinatorially selected T7 peptide (TLTTLTN). Accordingly, T7 molecules are attracted to the edges of nanocubes due to multiple times higher mobility of water molecules compared to center portions of the cube, accompanied by a unique match of polarizable atoms in T7 to the square pattern of epitaxial sites. Synthesis, characterization, and atomistic simulations showed a preference of peptide T7 towards {100} facets over {111} facets at intermediate concentration, that explains a higher yield of cubes. Similar arguments explain control principles for the growth of twinned versus single crystals. The ratio of {111} and {100} facets differs 60/40 (for twinned crystals) versus 35/65 (for single crystals) and peptides with adequately balanced adsorption strength to these facets at different nucleation stages elucidates the mechanism of twin formation. We systematically analyzed the ratio of {h k l} facets on Pd nanoparticles of dif (open full item for complete abstract)

Committee: Hendrik Heinz Dr. (Advisor); Alamgir Karim Dr. (Committee Member); Kevin Cavicchi Dr. (Committee Member); Ali Dhinojwala Dr. (Committee Member); Jutta Luettmer-Strathman Dr. (Committee Member) Subjects: Biochemistry; Chemistry; Condensed Matter Physics; Molecules; Nanotechnology

Doctor of Philosophy, The Ohio State University, 2004, Chemistry

Electroosmotic flow is studied by non-equilibrium molecular-dynamics simulations in a model system chosen to facilitate comparison with existing continuum theories. The model system consists of spherical ions and solvent, with stationary, uniformly charged walls that make a channel with a height of 20 particle diameters. We find that hydrodynamic theory adequately describes simple pressure-driven flow (Poiseuille flow) in this model. However, when combined with Poisson-Boltzmann theory to describe electroosmotic flow, the continuum theory fails in important situations. The failure is traced to the exclusion of ions near the channel walls resulting from reduced solvation of the ions in that region. When Poisson-Boltzmann theory is adjusted to account for the exclusion of ions near the walls, agreement with hydrodynamic theory is restored. Monte Carlo simulation using an all-atom potential model is applied to evaluate two crystal structures of low density methyl chloride monolayer that have been proposed based on diffraction experiments. The equilibrium configuration proposed by Morishige, Tajima, Kittaka, Clarke and Thomas was found to be lower in energy than an alternative structure proposed by Shirazi and Knorr. The first-order melting transition of the monolayer crystal was found to occur between 85K and 90K, in qualitative agreement with experiments. However, the melting point from simulations is lower than the experimental melting point of 120K. After melting, short-range order within the methyl chloride fluid phase was found.

Committee: Sherwin Singer (Advisor) Subjects:

Master of Science in Chemical Engineering, Cleveland State University, 2010, Fenn College of Engineering

Accurate values for thermodynamic properties throughout the fluid phase are a requirement for the design of separation processes. To date, very few pure substances have been completely characterized because of time and monetary constraints. Low cost computing power now permits complete determination of the thermodynamic properties of pure substances via molecular simulation. Molecular simulation is computational statistical mechanics. Benzene is an important industrial chemical and pharmaceutical precursor. It is the prototypical, symmetric, hexagonal molecule and is an ideal candidate for molecular simulation. The molecular models of three researchers in the field are submitted for Monte Carlo simulation in the virtual laboratories at Cleveland State University. All claim that their models best represent real benzene. The MC code used for experimentation measures 12 thermodynamic properties with associated errors, and derivatives of the residual Helmholtz energy with respect to density and temperature to order 4. The thermodynamic properties are used to generate a multiparameter fundamental equation of state that represents the model throughout the fluid phase. Thermodynamic properties from the three models are compared to the values from the Goodwin equation of state for benzene. A single model is chosen as the best representative of real benzene.

Committee: Rolf Lustig PhD (Advisor); D.B. Shah PhD (Committee Member); Orhan Talu PhD (Committee Member) Subjects: Technology

Doctor of Philosophy, Case Western Reserve University, 2011, Macromolecular Science and Engineering

We studied the self-assembly dynamics of two polymeric systems, block copolymer micelles and supramolecular polymer solutions using computer simulation. Dissipative Particle Dynamics simulations were applied to study the equilibrium properties, kinetics of micellization and equilibrium chain-exchange in A2B3 and A4Bx(x=4,6,8) diblock copolymer micelle solutions. The critical micelle concentration, micelle aggregation number distribution and micelle structure were found to agree well with previous experimental and theoretical studies. The time-evolution of micelles from unimers is found to follow three stages: unimer consumption, equilibration of the number of micelles progressing mainly by the fusion/fission mechanism and slow adjustment of the weight-average aggregation number by micelle fusion, unimer and small aggregate exchange. The effect of polymer concentration, hydrophobic interaction energy and block length on the kinetics of micellization were also considered. By performing micelle hybridization simulations, we found the equilibrium chain exchange follows a first-order kinetic process and the characteristic time, mainly determined by chain expulsion and does not depend on polymer concentration. The chain exchange characteristic time, τ, increases exponentially with core block length, NA and interaction parameter between blocks, χAB as τ ~ exp(0.67χABNA). We also found that in contrast to theoretical predictions, chain exchange between micelles occurs more rapidly for micelles with a longer corona-block length due to a higher compatibility of diblock copolymers and therefore a lower potential barrier for chain expulsion. Using coarse-grained molecular dynamics simulations we studied the equilibrium and rheological properties of dilute and semi-dilute solutions of head-to-tail associating supramolecular polymers with our newly-developed model for spontaneous reversible association. We found that for a given spacer length all shear-rate-dependent reduced visc (open full item for complete abstract)

Committee: Elena Dormidontova (Advisor); Alexander Jamieson (Committee Member); Jay Mann (Committee Member); Lei Zhu (Committee Member) Subjects: Polymers

Doctor of Philosophy (PhD), Ohio University, 2024, Physics and Astronomy (Arts and Sciences)

The primary focus of this dissertation is the study of carbon and coal, particularly its atomistic dynamics in the conversion process to graphite or carbon foams and its interactions with plastics. Given the intricate molecular structure of coal, initial research was conducted on simpler amorphous-phase carbon structures, including amorphous graphite, multi-shell fullerenes, and multi-walled carbon nanotubes, to leverage their physical properties for understanding coal chemistry. This foundational research provided insights into fundamental properties such as interatomic interactions, thermal conductivity, and mechanical characteristics. The dissertation, organized largely as a collection of published works, explores the formation, structure, and properties of layered carbons and coal. It includes practical applications, such as coal carbonization, graphitization processes, and the development of carbon-plastic composites. The comprehensive exploration of these topics offers significant contributions to both the fundamental understanding and industrial application of coal and amorphous carbon materials.

Committee: David Drabold (Advisor) Subjects: Condensed Matter Physics; Physics

Doctor of Philosophy, The Ohio State University, 2024, Chemistry

Investigating dielectric behavior in inhomogeneous systems remains an open question, despite significant progress with homogeneous systems like the continuum. This work shifts the paradigm, interpreting dielectric behavior through a molecular picture instead of a continuum one. Our investigation focuses on water's dielectric behavior near a spherical ion—a model widely applicable to biological processes and electrokinetics. We demonstrate that the total bound charge near an ion is identical for both continuum and molecular systems. While polarization charge density is confined to an infinitely thin layer in continuum systems, it distributes within a finite range near the ion in molecular systems. We derive the formulations of dielectric properties in terms of polarization charge density compatible with both continuum and molecular solvents. Furthermore, we critically discuss a theoretical approach to interfacial dielectric constant that was recently proposed and underscore the necessity of appropriate treatment of dielectric properties under periodic boundary conditions. Building on dielectric behavior, we explore ion solvation through molecular dynamics simulations. We propose a theoretical methodology for correcting the finite size effect inherent in the periodic boundary condition, without employing Ewald summation. This correction leads to a free energy value and the corresponding Born radius for an infinite system aligning with existing literatures. Through simulations and our methodology, we provide a physical interpretation of the Born radius in molecular systems. We unveil unique overcompensations from alternating charge layers near the ion, which converge to the Born radius further from the ion. It has been observed that the Born radius in molecular systems is smaller than the radius where solvent molecules begin to appear. To interpret this smaller Born radius, we utilize a simple model for cumulative bound charge, where (open full item for complete abstract)

Committee: Sherwin Singer (Advisor); Alexander Sokolov (Committee Member); Steffen Lindert (Committee Member) Subjects: Chemistry; Physical Chemistry

PhD, University of Cincinnati, 2023, Arts and Sciences: Chemistry

The intricate dynamics of molecular systems are pivotal to understanding numerous biological processes and have significant implications in biomedical research. This thesis presents a compre- hensive study of the behaviors of various molecular systems through molecular dynamics (MD) simulations, corroborated by empirical evidence from cutting-edge experimental techniques. The first part of the study investigates Sodium Dodecyl Sulfate (SDS), revealing the relaxation behaviors of SDS molecules through MD simulations. The congruence between the simulation results and empirical data from Nuclear Magnetic Resonance (NMR) experiments validates the simulation ap- proach, suggesting the potential for combined MD and NMR studies to explore molecule dynamics akin to SDS with high reliability. The thesis also delves into the complex functionality of the molecular chaperone ClpB, which is integral to protein disaggregation. By integrating single-molecule F ¨orster Resonance Energy Transfer (FRET) experiments with computational predictions from MD simulations, the research advances understanding of ClpB's conformational mechanics. Crucially, the optimization of MD force field parameters, informed by experimental data, enhances the accuracy of the protein dynam- ics representation. This optimized model captures the nuances of ClpB activity, providing a refined tool for examining protein disaggregation and signaling a leap forward in predictive simulations that could be applicable across the spectrum of protein dynamics research. Lastly, the thesis explores the role of the disaggregase nanomachine Hsp104 in protein home- ostasis through targeted MD simulations. The research elucidates a dual pathway in the mechanical unfolding of substrate proteins, exemplified by the green fluorescent protein (GFP), and underscores the influence of protein orientation on unfolding pathways. These insights into Hsp104's substrate (open full item for complete abstract)

Committee: George Stan Ph.D. (Committee Chair); Stephen Fox Ph.D. (Committee Member); Ryan White Ph.D. (Committee Member); Pietro Strobbia Ph.D. (Committee Member); Allison Talley Edwards Ph.D. (Committee Member); In-Kwon Kim Ph.D. (Committee Member) Subjects: Chemistry

Doctor of Philosophy, The Ohio State University, 2023, Mechanical Engineering

Nanotechnology is the use of matter on atomic, molecular, and supramolecular scales for industrial purposes. It consists of visualization, construction and manipulation material, molecules and atoms at the nano scale, but it is often complex and expensive to achieve targeted dynamic functions. Nanomechanical DNA origami devices are highly promising platforms or tools for achieving complex dynamic functions at the nanoscale. In particular, the assembly of dynamic nanomechanical DNA origami devices is a promising route to construct biomimetic or bioinspired materials that leverage the diverse properties and interactions of biomolecules. However, there is a need for enhanced design, assembly, and modeling approaches for dynamic DNA origami devices to realize their potential for nanomechanical applications. This work focused on developing hybrid assembly of dynamic DNA origami-peptide systems; a method of describing nanomechanical behaviors like force application based on simulation; design of complex compliant assemblies with tunable mechanical behavior; and molecular scale force sensing devices. Through these developments, I aim to expand usage of dynamic nanomechanical DNA origami devices, and establish a framework to design and build nanomechanical devices guided by simulation with both prescribed target geometry and mechanical functions. First, we leverage the interaction properties of coiled-coil peptides and the structural and dynamic properties of DNA origami to make hybrid DNA-peptide assemblies where reconfiguration of the DNA devices can regulate the structure and mechanical properties of higher order assemblies. Second, we establish a computational characterization of a dynamic device based on MD simulations including introducing the use of a virtual spring to analyze the force properties and a history-dependent bias to obtain free energy landscapes. Third, we create a tri-valent dynamic unit with potential capability to be constructed to high order structu (open full item for complete abstract)

Committee: Carlos Castro (Advisor); Hai-Jun Su (Committee Member); Jessica Winter (Committee Member); Jonathan Song (Committee Member) Subjects: Biomechanics; Mechanical Engineering

Doctor of Philosophy, The Ohio State University, 2022, Chemical Engineering

In molecular dynamics (MD) simulations, coarse grained force fields significantly reduce the computational burden when predicting the structural properties of materials, but negatively impact the resulting transport property predictions, typically accelerating the dynamic evolution of the system. Using the methods of equilibrium and non-equilibrium MD simulations, the nanoscale structure of neat polymer grafted-nanoparticle (PGN) assemblies deposited on a smooth surface, and the transport properties of simple linear ethers are explored. Specifically, generic coarse grained bead-spring models are used to reach the time and length scales associated with entanglements, and to isolate the effect of architecture on the nanoscale structure and chain conformations of entangled and hexagonally packed PGN monolayers, which consist solely of nanoparticles (NPs) protected by grafted polymer chains. At increased graft densities brushes are dryer and more aligned, with decreased interpenetration between chains on neighboring canopies. This leads to fewer interparticle entanglements per chain, which are increasingly localized to interstitial regions. Chains also have increased alignment normal to the NP surface at high graft density, and increased intraparticle entanglement density near the surface. The inverse relationship between graft density and the degree of interparticle entanglement of the brush suggests that higher graft density monolayers will have reduced toughness and robustness under strain. Understanding these relationships, and generally connecting experimentally tunable parameters to molecular-scale structure and overall material properties, will provide insight into optimal design of future materials. In the second part of the thesis, finer transferable atomistic and united atom force fields are used to better capture trends in diffusivity and apparent viscosity across a range of temperatures and shear rates for a series of linear ethers. Specifically, tren (open full item for complete abstract)

Committee: Isamu Kusaka (Advisor); Kurt Koelling (Committee Member); Lisa Hall (Advisor) Subjects: Chemical Engineering

Master of Science, Miami University, 2022, Chemical, Paper and Biomedical Engineering

The need for more efficient drug design and development has become more prevalent in just the last few years, leading to the development of the SAMPL challenges to promote exploration of methods to compute physical properties key to drug development. Blind predictions of octanol/water partition coefficients at 298.15 K for 22 drug-like compounds were made for the SAMPL7 challenge. The octanol/water partition coefficients were predicted using solvation free energies computed using molecular dynamics simulations, wherein we considered the use of both pure and water-saturated 1- octanol to model the octanol-rich phase. Water and 1-octanol were modeled using TIP4P and TrAPPE-UA, respectively, which have been shown to well reproduce the experimental mutual solubility, and the solutes were modeled using GAFF. After the close of the SAMPL7 challenge, we additionally made predictions using TIP4P/2005 water. We found that the predictions were sensitive to the choice of water force field. However, the effect of water in the octanol-rich phase was found to be even more significant and non-negligible. The effect of inclusion of water was additionally sensitive to the chemical structure of the solute.

Committee: Andrew Paluch (Advisor); Alim Dewan (Committee Member); Jason Boock (Committee Member) Subjects: Chemical Engineering

Doctor of Philosophy, The Ohio State University, 2021, Biochemistry Program, Ohio State

Development and functionality of multicellular organisms relies on precise and strong adhesion between cells. Members of the cadherin superfamily of proteins are involved in calcium-dependent cell-cell adhesion in animals and have been shown to play vital roles in various relevant biological processes. The cadherin superfamily can be largely classified into three subfamilies: the classical cadherins, the non-clustered protocadherins, and the clustered protocadherins. The typical cadherin protein consists of a single-pass transmembrane domain, a cytoplasmic domain, and multiple non-identical extracellular cadherin (EC) repeats. These ECs are defined by their Greek-key fold and an EC linker region with highly conserved calcium-binding sites. The binding of calcium helps to provide the rigidity necessary for proper protein-protein interaction. Within this work I focus on cadherins responsible for mechanotransduction, both from the classical and non-clustered subfamilies. Adherens junctions are formed by classical members of the cadherin superfamily and provide strong adhesion between cells. Past experiments have determined that interactions between individual cadherins are weak and therefore the strength provided by epithelial cadherin (CDH1), the major cadherin of adherens junctions, must come about through the formation of cadherin complexes. These cadherin complexes are composed of multiple CDH1 molecules binding through trans- (ectodomains originating from adjacent cells) and cis-interactions (ectodomains originating from the same cell) as seen in x-ray crystal structures and cryo-electron tomography images. While most experiments have focused on single homodimers, the mechanical unbinding events of cadherin junctional complexes and their effect on the membrane and associated cytoplasmic proteins remains unexplored. My work on CDH1 junctional complexes and their associated proteins utilizes large-scale all-atom molecular dynamics (MD) simulations to probe the ad (open full item for complete abstract)

Committee: Marcos Sotomayor (Advisor); Mark Foster (Committee Member); Steffen Lindert (Committee Member); Charles Bell (Committee Member) Subjects: Biochemistry; Biomechanics; Biophysics

Doctor of Philosophy (PhD), Ohio University, 2021, Chemical Engineering (Engineering and Technology)

Molecular dynamics (MD) simulation is a computational methodology to probe molecular-level details of physical systems. In MD, the motion of molecules is simulated and from the molecular trajectories, thermodynamic and kinetic properties are ascertained. Machine learning (ML) techniques are a set of computational tools that allow us to identify complex, non-linear relationships in data. ML methods are particularly useful when a system property of interest depends on a large number of variables, and there are no accurate physics-based models relating the property of interest to the variables. ML methods rely on the availability of large datasets to tease out the relationships between the variables. In this research, we have employed MD simulations to study the structural and thermodynamical properties of the simplified plasma membrane of eukaryotic cells, known as the lipid bilayer. We have applied ML methods to study the phase diagram of lipids. Furthermore, we have used ML methods for various corrosion-related applications. By studying asymmetric lipid bilayers using MD simulations, we have shown that in equimolar, asymmetric lipid bilayers, the two leaflets of the bilayer are in tensile and compressive mechanical stress. In response, cholesterol molecules redistribute between the leaflets to relieve these stresses. As a result, the distribution of cholesterol molecules depends on the relative ordering of lipids in the two leaflets. We show that there is a quantitative relationship between cholesterol distribution and the ordering of lipids. We have also studied the distribution of cholesterol molecules in lipid bilayers as a function of temperature and phase of the lipids. We have applied ML to study phase behavior in three-component lipid mixtures and have shown that trained ML methods are quite effective in reproducing the phase diagram of lipids. Furthermore, we have applied ML tools to model the time-dependent corrosion rate of mild steel in presence (open full item for complete abstract)

Committee: Sumit Sharma Associate Professor (Advisor); Douglas Goetz Professor (Committee Member); Gary Weckman Professor (Committee Member); Alexander Neiman Professor (Committee Member); Marc Singer Associate Professor (Committee Member) Subjects: Biomedical Engineering; Chemical Engineering

Master of Science, University of Akron, 2021, Polymer Science

A fundamental understanding of polymer translocation through nanopores is important for various biological phenomena such as the ejection of viral DNA and the transport of proteins, DNA, and RNA through membrane nanopores. Many factors control the phenomenon of polymer translocation. In the present study, we investigated the effect of polymer topology on translocation process. We employed the bead-spring model and Langevin dynamics to simulate poly[n]catenane passing through a nanopore under an external driving force. We varied the number of rings (n), number of beads per ring and also the stiffness of the polymer chain to investigate their relationship with the translocation process. In addition, other important factors such as the diameter and length of the nanopore are also varied and used to develop scaling laws for the translocation of poly[n]catenanes through nanopores.

Committee: Mesfin Tsige (Advisor); Toshikazu Miyoshi (Committee Member) Subjects: Polymers

Master of Science, University of Akron, 2021, Polymer Science

Graphene has been widely used in nanocomposites as reinforcement because of its excellent physical properties. Polyvinyl alcohol (PVA) is one of the common matrix polymers and it is favorable interaction with hydrophilic reinforcement is attributed to its hydrogen bonds. However, investigating the structure of the buried interface through traditional experimental characterization methods is quite challenging. Molecular-level simulations have been very helpful in characterizing buried interfaces such as the molecular structure, hydrogen bond effect, orientation, etc. In the present study, using molecular dynamics simulations, we investigated the structure and dynamics of polyvinyl alcohol molecules near single-layer graphene. The effect of polymer chain length, temperature, and the distance between the confining graphene layers on the structure and dynamics of PVA chains have been investigated.

Committee: Mesfin Tsige Dr. (Advisor); Toshikazu Miyoshi Dr. (Committee Member) Subjects: Polymers

Doctor of Philosophy (PhD), Ohio University, 2021, Chemistry and Biochemistry (Arts and Sciences)

The T-box riboswitch is a cis-acting regulator RNA element found primarily in the 5′ untranslated region of Gram-positive bacterial mRNAs that code for aminoacyl synthetases and other amino acid-related genes. Many of these genes are essential to the survival of the respective bacteria. The T-box riboswitch functions as a two-part system containing an aptamer domain and expression platform that together regulate transcription or translation. A gene-specific uncharged tRNA functions as the effector ligand by binding in the aptamer domain resulting in transcription readthrough (or translation initiation). The presence of the T-box riboswitch only in bacterial and not mammalian cells makes it an interesting drug target, however targeting specific RNA constructs remains a major challenge. Identifying small molecules that can bind discriminately to specific RNA secondary and tertiary structures requires strategically designed prediction models. In this study, combinatory compound screening using molecular modeling and moderate throughput assays was used to identify `hit' compounds that could be studied further with the potential to design ideal small molecule inhibitors. The potential role of T-box riboswitch agonists like polyamines, which are ubiquitous in binding to nucleic acids, to mimic in vivo conditions in vitro was investigated to help identify compounds of interest early in the screening process. Using optimized primary screening assays, a natural products library, RNA-targeted synthetic compounds, and computational methods (e.g., docking, molecular dynamics); a strategy for developing a pharmacophore model for the T-box riboswitch was established. The combinatory screening approach developed could be used for other structured RNA targets of interest. A pharmacophore workflow was designed with iterative improvements assisted by molecular dynamic simulations to obtain a validated pharmacophore model. The molecular dynamic simulations were initially optimized usi (open full item for complete abstract)

Committee: Jennifer Hines PhD (Advisor) Subjects: Biochemistry; Chemistry

Doctor of Philosophy, University of Akron, 2020, Polymer Science

Molecular dynamics is a robust research tool to investigate both bulk and interfacial phenomena. The current manuscript detailed two all-atom simulation studies. The first involves a developing work on the use of linoleic acid as a bio-oil asphalt modifier. Measurements were made on glass transition temperature, molecular mobility, viscosity, and species dispersion. Important trends were identified with potential optimality at moderate additive loading percentages. Barring the challenge in bridging the large order of magnitude difference between computationally accessible and mixing plant shear rates, a technique was detailed whereby mixing and compaction temperatures can be retrieved from construction manuals. The processing temperature reduction implications of correctly characterizing the non-Newtonian flow behaviors of modified asphalt are quantitatively and qualitatively discussed. Further, the single fatty acid species study can serve as a springboard for studies that involve diverse fatty acids with comparable compositions to those that exist in bio-oils like soybean oil and corn oil. To this effect, plausible asphaltic molecular designs were forwarded. This second part of the manuscript covers different aspects of carbon nanotube (CNT) – driven adsorption. Structurally simple yet with amphiphilic properties shared by a wide range of organic contaminants, benzoic acid was chosen as a probe adsorbate molecule. Benzoic acid attained optimal packing orientation in the adsorption region – an iv effect that propagated even outside the adsorption region when there are few or no surface oxygens. By carefully accounting for the multi-way interactions in the adsorption region peculiar mass accumulation trends were observed and explained. Carboxyl-carboxyl associations born of hydrogen bonds were proposed as providing stability to the adsorbed benzoic acid on tube exteriors. These associations were found to be secondary to the dominant aromatic-aromatic interactions (open full item for complete abstract)

Committee: Mesfin Tsige (Advisor); Yu Zhu (Committee Chair); Ali Dhinojwala (Committee Member); Hunter King (Committee Member); Jie Zheng (Committee Member) Subjects: Materials Science; Polymer Chemistry; Polymers

Doctor of Philosophy, Case Western Reserve University, 2020, Chemical Engineering

Solute-vacancy interactions and grain boundary structure and dynamics in an MgO crystal are investigated through molecular dynamics simulations. For the first time using molecular dynamics simulations, the binding entropy and enthalpy are determined directly for a solute-vacancy system in a single crystal of magnesium oxide, with a binding entropy of 13±5 (95% CI) J/mol K. The binding energy is also shown as a function of pressure. The method of (Sastry, Debenedetti, Stillinger, et al.) to quantify structure in glasses is applied to simulations of MgO grain boundary structures to identify equilibrium grain boundary structure and grain composition. The dynamical exchange of atoms within the grain boundary is demonstrated. The grain boundary diffusion coefficient is obtained as a function of temperature and pressure, and implications for grain boundary diffusion and transport through the inner earth are presented, with the result that the characteristic grain boundary diffusion length is constrained to be less than about 100 m for magnesium and oxygen at the core-mantle boundary. Finally, the transition between effective volume diffusion and effective grain boundary diffusion is obtained as a function of temperature and pressure.

Committee: Lacks Daniel PhD (Advisor); Van Orman James PhD (Committee Member); Gurkan Burcu PhD (Committee Member); Wirth Christopher PhD (Committee Member) Subjects: Chemical Engineering; Geology; Geophysics; Molecular Physics; Molecules; Solid State Physics

PhD, University of Cincinnati, 2020, Arts and Sciences: Chemistry

The nanomechanics of heat shock protein (70 kDa) and the mechanical properties of the microtubule lattice were investigated with coarse-grained molecular pulling and indentation simulations, respectively. Heat shock protein is a molecular chaperone known for its role in folding nascent peptides as they exit the ribosome and preventing protein aggregation. Preventing protein aggregation is critical for combating neuro-degenerative diseases like Alzheimer's and Parkinson's disease. We uncovered mechanical rigidification in the substrate binding domain and lobe II of the nucleotide binding domain upon hydrolysis. We found that this rigidification was communicated allosterically and through noncontiguous residues of the protein's subdomains contrary to the literature previously indicating the interdomain linker as the means of allosteric communication. Concerning my other areas of research, the investigations into microtubule severing by severing proteins like katanin, we discovered important mechanical properties pertinent for how microtubule severing occurs. Katanin is a severing protein expected to target microtubule lattice defects in order to induce severing. The seam was thought to be a lattice defect. Understanding how severing proteins interact with the microtubule lattice permits scientists to better understand and eventually manipulate or control cellular division. With this understanding, they can better develop and engineer pharmaceutical drugs capable of diverting, interrupting, or even accelerating the severing process. By comparing the force of indentation on and around the seam, we were able to eliminate from consideration the seam as a microtubule defect by comparing and identifying similar distributions of critical breaking forces on and off of the seam.

Committee: Ruxandra Dima Ph.D. (Committee Chair); Bruce Ault Ph.D. (Committee Member); Anna Gudmundsdottir Ph.D. (Committee Member) Subjects: Biophysics