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

Here we present investigations on the structure and mechanics of molecular force sensors and DNA nanodevices using a combination of computational and experimental approaches. This work implements a range of methods from all-atom and coarse-grained molecular dynamics to cryogenic and transmission electron microscopy. All-atom molecular dynamics simulations were employed to characterize the mechanical properties of peptide-based and DNA-based molecular force sensors. The simulations revealed that the stiffness of peptide-based sensors, derived from spider silk or synthetic peptides, is consistent with theoretical predictions and experimental measurements. However, the formation of transient secondary structures in spider silk-based sensors and overstretching in DNA-based sensors can influence their elastic responses, highlighting the importance of considering these factors in sensor design. The research also explored the use of DNA origami nanostructures for delivering gene templates for homology-directed repair (HDR) in human cells. Coarse-grained simulations (oxDNA) guided the design of DNA nanostructures, and experiments demonstrated their efficacy in enhancing HDR efficiency compared to unstructured DNA, particularly when delivered using Cas9 virus-like particles (VLPs). This finding suggests the potential of DNA nanostructures for targeted gene delivery and genome editing applications. Furthermore, the dissertation explored the development of DNA-origami-protein hybrid devices for cryogenic electron microscopy characterization of protein interactions and force spectroscopy applications. Preliminary data demonstrated the feasibility of integrating peptide-based force sensors into DNA nanostructures, which is a step toward enabling the real-time measurement of mechanical forces applied to proteins. These hybrid devices hold promise for studying protein mechanics, folding, and interactions at the nanoscale, with potential applications in biomedical research, for (open full item for complete abstract)

Committee: Marcos Sotomayor (Advisor); Carlos Castro (Advisor) Subjects: Biophysics

Doctor of Philosophy, The Ohio State University, 2024, Chemical Engineering

Polymers have gained attention for their use as solid electrolytes in lithium-ion batteries due to their high energy density and enhanced safety. To increase cation conductivity in solid-state polymer electrolytes, particularly at room temperature, a range of polymer systems have been explored extensively in recent years. Understanding the ion behavior in polymer systems at the molecular level is essential. Generic coarse-grained bead-spring models are widely used to describe polymeric systems in molecular dynamics simulations, which have demonstrated qualitative consistency with a variety of structural and dynamic results from experiments. When ions are present, additional model features are needed to account for their longer-ranged interactions with each other (typically through Coulomb interactions within a uniform dielectric constant background) and for their interactions with polarizable polymers. For example, using additional pairwise potentials or embedding the classic Drude oscillator to achieve polarizable modeling. One objective of this research is to study the ion behavior across various polymer systems by employing a pairwise solvation potential. Additionally, this study aims to develop the Drude oscillator integrated model in coarse-grained polymer simulations to study ion-containing polymer electrolytes. We first studied the single-ion block copolymers, which are gaining interest as potential electrolytes with high cation transference numbers. Because anions are tethered to the polymer chains, the cation transference number, which is the fractional contribution of cation conductivity to overall ion conductivity, is unity in the limit that transport of the polymer chains is negligible. Such a high transference number is of interest in reaching a high charging rate and avoiding concentration polarization that is possible in salt-doped systems. However, tethered anions may decrease polymer and cation dynamics and thus reduce cation conduction. To (open full item for complete abstract)

Committee: Lisa Hall (Advisor); Xiaoguang (William) Wang (Committee Member); Isamu Kusaka (Committee Member) Subjects: Chemical Engineering

Doctor of Philosophy, The Ohio State University, 2023, Biophysics

Cadherins are a family of large transmembrane glycoproteins instrumental in facilitating organ formation during morphogenesis in vertebrates and invertebrates. At the cellular level, they are involved in adhesion, signaling, recognition, mechanotransduction, and motility. In the modern classification of the cadherin superfamily, classical cadherins with five extracellular cadherin (EC) repeats as well as clustered and non-clustered -protocadherins with six or seven EC repeats have been well-studied and their homophilic/heterophilic interactions with molecules on the same (cis) cell or opposite (trans) cells have been characterized. Complexity arises when the number of EC repeats increases with diverse Ca2+ coordination at linker regions between two consecutive EC repeats. In larger cadherins, such as cadherin-23 (CDH23), protocadherin-15 (PCDH15) and cadherin epithelial growth factor (EGF) Laminin-G (LAG or LamG) seven pass G-type receptor-1 (CELSR1), the structural flexibility afforded by different Ca2+ coordination plays determinant roles in their adhesion capacity during inner-ear mechanotransduction and planar cell polarity (PCP). CDH23 and PCDH15, each with 27 and 11 EC repeats, connect two adjacent hair- like protrusions known as stereocilia together atop of a hair cell, the primary mechanosensory cell in the inner ear. Through heterophilic interactions between their first two N-terminal EC repeats, CDH23 and PCDH15 form a filament known as the tip link. In response to sound, stereocilia undergo displacement and the tip link experiences tension, which opens the ion-conducting mechanotransduction channels on the tip-link's lower end to send signals to the brain. The heterophilic trans tetrameric complex formed by CDH23 and PCDH15, and the cis interactions along the length of PCDH15 have been well-studied in the past but full-length ectodomain structures and high-resolution structural models of complete CDH23 and PCHD15 ectodomain have not been resolved. H (open full item for complete abstract)

Committee: Marcos Sotomayor (Advisor) Subjects: Biochemistry; Biophysics

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

Severe heat shock, cellular stress, and mutations can cause massive protein misfolding and aggregation, resulting in the loss of essential cellular activity. ClpB is a double-ring hexameric structure that contains two AAA+ (ATPases Associated with diverse cellular Activities) nucleotide binding domains (NBDs) per protomer. Threading of substrate proteins through the narrow central pore is promoted through the application of mechanical force by central pore loops (PLs) in repetitive allosteric cycles of ClpB. Despite recent advancements in ClpB studies, it is still unclear how ClpB performs its disaggregation activity. In the prokaryotic cell, energy-dependent proteases are essential in controlling metabolic pathways and the cell cycle. The ClpP peptidase oligomerizes as two stacked heptameric rings and encloses a degradation chamber. To ensure selective degradation, substrate protein access to the chamber is controlled by a gating mechanism of its axial pore, which involves conformational transition of N-terminal loops of ClpP subunits. Even though ClpP conformations have been studied extensively, it is still unclear about the mechanism of allosteric communication in the gating mechanism. I present three studies to address the issues mentioned above. First, I performed all-atom molecular dynamics simulations for two distinct conformations, "ring" and "spiral" to study the asymmetric conformational dynamics of ClpB. The analysis indicates that the ClpB hexameric pore is stabilized by a network of inter-protomer salt bridges formed by the conserved pore loops located in the central channel. Clustering of dynamic motions suggests strong inter-protomer collaboration between domains of neighboring protomers in the asymmetric hexamer. Collective motions, investigated using Principal Component Analysis, reveal the importance of axial motions of the central pore loops are in agreement with the substrate translocation mechanisms of ClpB identified in experimental studies. I (open full item for complete abstract)

Committee: George Stan Ph.D. (Committee Chair); Ryan White Ph.D. (Committee Member); In-Kwon Kim (Committee Member) Subjects: Biophysics

Master of Science in Mechanical Engineering (MSME), Wright State University, 2022, Mechanical Engineering

This study uses molecular dynamics simulations to evaluate the dynamic behavior of a partially wetting polymer droplet driven over a nanostructured interface. We consider the bead-spring model to represent a polymeric liquid that partially wets a rough surface composed of a periodic array of spherical particles. Results show that at sufficiently small values of external force, the droplet remains pinned at the particle's surface, whereas above the threshold its motion consists of alternating periods of pinning and rapid displacements between neighboring particles. The latter process involves large periodic variation of the advancing and receding contact angles due to the attachment and detachment of the contact line. Finally, upon increasing the external force, the droplet's center of mass is steadily displaced, while at the same time the oscillation amplitude of the receding contact angle as well as the maximum contact angle hysteresis remain relatively unchanged.

Committee: Nikolai V. Priezjev Ph.D. (Advisor); Ahsan Mian Ph.D. (Committee Member); Sheng Li Ph.D. (Committee Member) Subjects: Materials Science; Mechanical Engineering; Nanoscience

Doctor of Philosophy, University of Akron, 2022, Chemistry

Methanotrophic bacteria absorb methane and oxidize it as their sole source of carbon and energy. Almost all methanotrophic bacteria contain an extensive network of Intracytoplasmic membrane (ICM). The ICMs contain particulate methane monooxygenase (pMMO), which is the initial enzyme in the metabolism of methane. Due to the accumulation of high lipid content in the form of ICM and the formation of polyhydroxybutyrate (PHB), there is a growing interest in utilizing these bacteria to convert the ICM and PHB to biofuel. Structural aspects of the ICM have been characterized by transmission electron microscopy. However, the dynamics and functional role of ICMs remain elusive. A rapid fluorescence microscopy method to visualize ICMs in situ using lipophilic dyes was developed in Chapter III. The extent to which ICM formation occurs in cells depends on the concentration of copper. The ICM formation was visualized and quantified in type I methanotroph Methylotuvimicrobium alcaliphilum (comb. Nov. 20Z) by tracking the bulk copper conversion spectroscopically and by live single-cell confocal imaging. Both methods showed a lag phase prior to the increase in ICM amounts over time. During the ICM formation, there was a significant amount of cell to cell heterogeneity. Further, rapid in-vivo quantification of the PHB method was developed to determine the conditions that enhance the PHB accumulation in methanotrophs. A rapid and cost-effective single cell PHB analysis through fluorescence microscopy by staining via Nile Blue A (NBA) in type II methanotroph Methylocystis sp. Rockwell was described in Chapter IV. NBA stained both the outer membrane of the cell and individual granules of PHB, distinctly but not the ICMs. The ICMs in Methylocystis. sp. Rockwell resides peripheral to the inner membrane whereas PHB is present in the cytoplasmic region. Methylocystis sp. Rockwell accumulated PHB when grown in ammonium mineral slats (AMS) medium, regardless of nitrogen or carbon stress. PH (open full item for complete abstract)

Committee: Adam Smith (Advisor); Sailaja Paruchuri (Committee Member); Nic Leipzig (Committee Member); Chrys Wesdemiotis (Committee Member); Yi Pang (Committee Member) Subjects: Biology; Chemistry

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

Developments of green energy alternatives (e.g., ethanol) and advanced CO2 capture technologies play a crucial role in solving the energy and climate crisis. Specifically, membrane-based separation processes provide opportunities as potentially energy-efficient means to extract alcohols or capture CO2. For alcohol extraction, ultrathin-film nanoporous membranes such as zeolite nanosheets may offer large separation factors and high fluxes because of their selective ethanol-to-water adsorption and short diffusion pathway. However, systematic investigations of potential nanosheet candidates are still missing to date, while atomistic understandings of their separation mechanism and structure-property relationship remain limited. For CO2 capture, facilitated transport membranes (FTMs) that utilize reversible chemical reactions between amino groups and CO2 have been demonstrated to offer notably enhanced selectivity and permeance. However, molecular understandings of the reactive diffusion mechanism of CO2 in the FTMs remain limited. This dissertation conducts computational studies to study membrane materials for ethanol separation and CO2 capture. Specifically, in Chapter 2, a screening study of zeolite nanosheets as pervaporation membranes for ethanol separation is discussed to show their separation performance and shed light on the relationship between separation factors, adsorption selectivities, and structural features. In Chapter 3, understandings achieved in the previous chapter are applied to study the alcohol/water pervaporation separation using zeolite membranes with various Si/Al ratios. Key factors identified in Chapter 2, such as surface silanol density and adsorption selectivity, are again shown to play an important role, which rationalizes the separation performance observed experimentally. Aside from zeolite materials, metal-organic frameworks (MOFs) have emerged as a promising class of nanoporous materials as membrane candidates. In order to facilitate (open full item for complete abstract)

Committee: W.S. Winston Ho (Advisor); Nicholas Brunelli (Committee Member); Li-Chiang Lin (Advisor) Subjects: Chemical Engineering

PhD, University of Cincinnati, 2021, Arts and Sciences: Chemistry

The exploration and quantification of functional group effects are essential in developing novel materials for energy storage and pharmaceutical applications. As methods for prototyping new materials become more readily available, testable criteria for material optimization are needed. Challenges associated with creating these criteria lie with the difficulty of observing the microscopic behaviors that drive desirable macroscopic phenomena. In this work, I demonstrate the usage of various computational techniques to preform these observations directly. The two fields examined in my work (energy storage and species transport/encapsulation) can be related by their reliance on hydrogen-bond forming functional groups (or the elimination of these groups) to modulate their performance. This thesis makes the case that these hydrogen-bond forming groups are a driving factor for a system's performance and sometimes need to be modeled using sophisticated methods such as ab initio molecular dynamics (AIMD). In the specific field of energy storage this work contains the comparison of results from fit-by-analogy classical, experimental-fit classical, and AIMD simulations. Examining their ability to model the key interactions in glycerol carbonate electrolyte systems displays the shortcomings of both classical methods. The AIMD results of this work display that unique ion-pairing configurations can have large effects on the physicochemical properties of a liquid, and that the nature of the ion affects the medium-range structuring of the surrounding solvent. If this medium-range structuring is important to the macroscopic properties of the liquid, then the modeling of the solvent becomes that much more important, and treating charge transfer accurately between the ion and first two solvent shells may play a large part in the successful modeling of these liquids.

Committee: Thomas Beck Ph.D. (Committee Chair); George Stan Ph.D. (Committee Member); Yujie Sun Ph.D. (Committee Member) Subjects: Chemistry

Doctor of Philosophy, The Ohio State University, 2020, Chemical Engineering

Solid polymer electrolytes are attractive for use in batteries due to their ease of fabrication, electrochemical stability, and mechanical robustness. However, their low ion conductivity leads to insufficiently low charge/discharge rates for many applications. Our research employs coarse-grained molecular dynamics (MD) simulations to understand ion transport in both salt-doped homopolymers and block copolymers under different conditions, to aid the design of future materials with improved conduction. We first focused on how copolymer nanostructures affect particle diffusion using MD simulations and constrained random walk analysis. Diffusion through randomly oriented grains is 1/3 for cylinder and 2/3 for lamellar morphologies versus an homopolymer system, as previously understood. Diffusion in the double gyroid structure depends on volume fraction and is 0.47-0.55 through the minority phase at 30-50 vol.% and 0.73-0.80 through the majority at 50-70 vol.%. Thus, among randomly oriented standard minority phase structures with no grain boundary effects, lamellae is preferable for transport. Then, we applied a coarse-grained model that includes a 1/r4 potential form to represent ion solvation, allowing us to reproduce experimental behavior of ion diffusion in block copolymers and explore their molecular underpinnings. We show that the trend of increasing diffusion with molecular weight becomes more dramatic as ions are solvated in one polymer block more strongly or as the ion-ion interactions get stronger. In contrast to expectations, the interfacial width or the overlap of ions with the nonconductive polymer block do not adequately explain this phenomenon; instead, local ion agglomeration best explains reduced diffusion. Interfacial sharpening, controlled by the Flory parameter and molecular weight, tends to allow ions to spread more uniformly, and this increases their diffusion. To better understand correlated anion and cation motion, which c (open full item for complete abstract)

Committee: Lisa Hall (Advisor); Li-Chiang Lin (Committee Member); Isamu Kusaka (Committee Member) Subjects: Chemical Engineering

Master of Science, The Ohio State University, 2020, Chemistry

Molecular dynamics simulations are widely used to study dynamics of molecular structure. The impact of molecular dynamics simulation in the field of chemistry and biology has expanded drastically in past decade. The simulations capture properties and behavior of biological macromolecules at atomistic level with a fine temporal resolution. Molecular dynamics simulations use implicit and explicit solvents. Explicit solvents are more accurate but add to the size of the simulation box, limiting the duration of simulations to hundreds of µs. To be able to study MD systems at larger time scale we introduce a neural network-based method that uses solute coordinates to output solvation energy and in turn giving the forces exerted by solvents. Using the amino acids and their dipeptide coordinates, interatomic distances were calculated and used in the neural network to get energies. Out of twenty amino acid dipeptides, six amino acid dipeptides, ALA, TYR, ASP, GLN, LYS and GLY gave an energy difference average of ~100 kJmol-1.

Committee: Rafael Bruschweiler Prof (Advisor); Marcos Sotomayor Dr (Committee Member) Subjects: Chemistry

Master of Science, University of Akron, 2019, Physics

Motor proteins are molecular motors capable of active movement within cells. The motor protein kinesin plays an integral role in cell function, transporting, for example, cargo from the center to the periphery of a cell. Kinesins are composed of two heads, two neck linkers, and a coil connecting these parts to the carried cargo. Kinesin molecules have been shown experimentally to walk along tubulin-based protein structures called microtubules in a hand-over-hand stepping motion, carrying their cargo eight nanometers per step. However, details of the stepping process, including the role of the neck-linkers, are still under investigation. They are difficult to study with atomistic simulations due to the size of the proteins and the long time-scales involved. In this work we develop a 3D model of kinesin stepping on a rigid microtubule substrate that can be simulated efficiently with Brownian dynamics simulations. The geometric parameters of our five-site kinesin model reflect the geometry of a kinesin motor protein. The interactions governing the motor protein conformations and the interactions between kinesin sites and the microtubule sites are designed to reproduce important aspects of the biological system. We perform simulations spanning many kinesin steps to investigate the stepping efficiency of the motor protein. To compare with experiments, we study kinesin motors with neck linkers of different lengths. We find that neck linkers close to the wild-type length have the highest stepping efficiency, about 90%, in agreement with experimental data. In addition, we find that increasing the neck-linker length leads to a decrease in efficiency, as has also been observed in experiments.

Committee: Jutta Luettmer-Strathmann Ph.D. (Advisor); Alper Buldum Ph.D. (Committee Member); Yu-Kuang Hu Ph.D (Committee Chair) Subjects: Biophysics; Molecular Biology; Physics; Theoretical Physics

Doctor of Philosophy, The Ohio State University, 2019, Chemical Engineering

Ultrathin films containing neat polymer-grafted nanoparticles (PGNs) show promise for designing next-generation printed electronics and energy storage devices. Our research utilizes molecular dynamics (MD) simulations to understand the structure, entanglements, and mechanical properties of adsorbed neat PGN particles with varying graft density and polymer length, to provide insight towards the rational design of robust materials with precise spacing of inorganic particles. We first simulate individual and pairs of PGNs adsorbed to a surface with varying monomer-surface interactions. For individual PGNs, increasing the monomer-surface adsorption strength causes the polymer chains to spread out to increase contact with the surface, which agrees qualitatively with recent experimental findings. 2D density profiles and radial distribution functions are used to show the combined effect of polymer length and graft density on the monomer packing and canopy shape at various adsorption strengths. A more detailed entanglement analysis is then developed to analyze interparticle entanglements. Pairs of PGNs show increasing particle spacing and decreasing interparticle entanglements with increasing monomer-surface interaction strength. Monolayers of PGNs in a hexagonal spacing are simulated at a favorable surface interaction strength. High graft density particles remain well-structured in the monolayer; however, the moderately grafted particles are less organized due to increased exposure of the nanoparticle surface and is more apparent at weaker monomer-surface interaction strengths. The extent of interpenetration is quantified and shows that moderately grafted PGN particles are more interdigitated than their high graft density counterpart, which results in an increase in interparticle entanglements. Uniaxial deformation of the monolayer displays an increase in strain at failure, and therefore robustness, for moderately grafted particles due to increased interdigitation an (open full item for complete abstract)

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

PhD, University of Cincinnati, 2019, Arts and Sciences: Chemistry

The physical properties of surfactant and amphiphile aggregate structures, for example folded globular proteins or surfactant solutions, are strongly modulated by changes in their aqueous environment such as solvated molecules, ions or solid substrates. The ability to study at a molecular level the structure and dynamics in these systems can aid in understanding the origin of many important properties and interactions ranging from medical implant biofouling to the activity of enzymatic scaffolds to the viscosity and stability of formulated soaps and detergents. To that end, I address two issues pertaining to these types of problems in this dissertation. In part I of this thesis, I use coarse-grained implicit solvent Langevin dynamics simulations to probe the unfolding of three protein fold motifs: an all-alpha four-helix bundle, a four strand beta barrel, and a mixed fold alpha/beta structure. These three protein folds are then placed near three hydrophobic surfaces: a planar hexagonal graphene-like structure and two curved hexagonal carbon nanotube-like surfaces. For the curved surfaces the radii of the tubes are created either with a relatively large or small radius and placed in a linear arrangement resulting in deep or shallow grooves. The proteins are initially oriented in several rotational states for each surface. My results indicate that binding and unfolding occur by different mechanisms depending on both the protein fold, its original orientation with respect to the surface and the topological character of the surface. Specifically, all-alpha four-helix bundle and the four strand beta barrel have competing stability profiles, where the four-helix bundle is more stable in the presence of curved surfaces and the beta barrel is stabilized in planar environments. This led to an interesting result with the alpha/beta fold, where the surface topology and initial orientation of the protein led to stable partially folded states following the trends found in th (open full item for complete abstract)

Committee: George Stan Ph.D. (Committee Chair); Thomas Beck Ph.D. (Committee Member); Charles Eads PhD (Committee Member); Anna Gudmundsdottir Ph.D. (Committee Member) Subjects: Physical Chemistry

Master of Science in Renewable and Clean Energy Engineering (MSRCE), Wright State University, 2018, Mechanical Engineering

In this thesis, the effects of the external pressure and surface energy on stability and wetting transition at nanotextured interfaces are studied using molecular dynamics and continuum simulations. The surface roughness of the composite interface is modeled via an array of spherical nanoparticles with controlled wettability. It was found that in the absence of external pressure, the liquid interface is flat and its location relative to the solid substrate is determined by the radius of the particle and the local contact angle. With increasing pressure on the liquid film, its interface becomes more curved and the three-phase contact line is displaced along the spherical surface but remains stable due to the re-entrant geometry. It was demonstrated that the results of molecular dynamics simulations for the critical pressure of the Cassie-Baxter wetting state agree well with the estimate of the critical pressure obtained by numerical minimization of the interfacial energy using Surface Evolver.

Committee: Nikolai Priezjev Ph.D. (Advisor); Hong Huang Ph.D. (Committee Member); Sheng Li Ph.D. (Committee Member); Ahsan Mian Ph.D. (Committee Member) Subjects: Engineering; Fluid Dynamics; Nanoscience; Nanotechnology

Doctor of Philosophy, The Ohio State University, 2018, Chemical Engineering

Ionomers are polymers that contain a small fraction of ionic groups covalently bound to a non-polar backbone. These bound ions along with free counterions tend to aggregate strongly in a low dielectric medium, giving rise to material properties different from the parent, uncharged polymer. Our research employs molecular dynamics (MD) simulations to understand the structure and dynamic behavior of these ionic aggregates under different conditions, to aid the development of improved materials such as ionomer composites for 3D printing. Prior work had established a useful CG model for acetic acid based ionomers, which we used in our work. First, we considered fully neutralized systems and applied uniaxial tensile deformation to understand the impact that aggregate morphology has on the mechanical properties of ionomers. The degree to which chains and ionic aggregates align was quantified; chains align significantly in response to deformation, while ionic aggregates are not as clearly aligned. The location of the ionomer peak (measure of interaggregate correlation) was tracked, and it was found that the length scale of aggregate order increases in the direction parallel to strain and decreases in the direction perpendicular to strain. The prior model for fully neutralized systems included COO– and Na+ but no COOH groups. To better model typical experimental systems that are only partially neutralized, we added additional `sticker' groups that represent COOH. These stickers are similar to uncharged monomer beads but with adjusted short ranged interaction strengths with each other and with ionic groups. Aggregate morphologies obtained using the sticker-based model are in good agreement with prior atomistic simulation results. Rheological properties were calculated, and were found to be in good agreement with experimental trends. A static electric field was applied to these partially neutralized ionomers. Aggregate morphology under the field was analyzed and compa (open full item for complete abstract)

Committee: Lisa Hall (Advisor); Stuart Cooper (Committee Member); Vishnu Sundaresan (Committee Member) Subjects: Chemical Engineering

PhD, University of Cincinnati, 2017, Arts and Sciences: Chemistry

Microtubules (MTs), polymerized from dimer units, are the main cytoskeletal filaments providing structural support for cells. The reorganization of MTs is often initiated by removing dimers through mechanical destruction of motor enzymes, such as katanin and spastin severing enzymes. Those enzymes convert chemical energy from ATP hydrolysis into mechanical work. The previous experimental work suggests that lattice defects act as active spots for those enzymes working on the MT lattice. In our research, we investigate the mechanical behavior leading to the crushing and recovering of MTs through using molecular dynamics simulations. Our in-silico experiments provide details of the MT breaking pathways at the molecular level as well as the distribution of mechanical forces needed to break the lattice. Our results strongly confirm the proposal that defects represented by lattice vacancies are important in MT crushing, as the force needed to break a filament with vacancies is much lower than it required to break an intact one. We obtained an exact match between our results and their experimental counterparts, including the force response, the breaking pathways and the respective kinking angle distributions, etc. We also studied the recovery process of MTs with or without vacancies and in the presence and absence of constraints. Our results indicate that constraints prevent MTs from fully recovering, particularly for a lattice with a high degree of vacancies. Taken together with the pushing studies, our lattice recovery data highly demonstrate the assumption that vacancies in the filament can weaken the MT stability and serve as targets for MT severing enzymes. We probed mechanical properties of the seam, which is usually considered as an inherent structural flaw in MTs. However, in our records, the seam behaved similarly as other lattice interfaces did in indentations as well as retractions. All the evidence convincingly demonstrated that the seam, although structurally (open full item for complete abstract)

Committee: Ruxandra Dima Ph.D. (Committee Chair); Thomas Beck Ph.D. (Committee Member); Laura Sagle Ph.D. (Committee Member) Subjects: Physical Chemistry

Doctor of Philosophy (PhD), Ohio University, 2017, Physics and Astronomy (Arts and Sciences)

Generating computer models of materials that faithfully represent all of our current state of knowledge about those materials has remained an unsolved problem. In particular, models of amorphous solids following from a molecular dynamics (MD) simulation commonly show structural defects and related mid-gap electronic states that are not present in the real materials. In this dissertation, we present a novel way of using a priori knowledge of the electronic band gap of amorphous systems to guide MD simulations. This involves computing Hellmann-Feynman forces associated with certain electronic states and judiciously coupling them to the total force in MD simulations. We show that such a method can provide a means to purge structural defects. By producing a series of models of amorphous carbon with varying sp2/sp3 ratio, we'll show that this method offers useful new flexibility in modeling. And, we demonstrate, for the first time, how MD simulations can be biased to systematically model an insulator-metal transition in glassy systems. The nature of electron transport in eSe3Ag glass is explored using advanced methods and important inferences are drawn about the role of Ag atoms in electronic conductivity. In particular, it is shown that a certain Se-Ag phase in this glass plays a dominant role in electron transport. We also investigate the response of a-GeSe3Ag to radiation damage using empirical interatomic interactions and show that the glass exhibits rapid recovery after a knock on event. Finally, we consider the the coupling between lattice vibrations and electronic states in disordered systems and show that disorder induced localization of states dictates the thermal modulation of electronic energy.

Committee: David A. Drabold (Advisor); Sumit Sharma (Committee Member); Eric Stinaff (Committee Member); Gang Chen (Committee Member) Subjects: Condensed Matter Physics; Physics

Doctor of Philosophy, The Ohio State University, 2016, Chemistry

Functional protein motions covering a wide range of timescales can be studied by NMR and molecular dynamics (MD) computer simulations. Nuclear magnetic resonance (NMR) spectroscopy of uniformly 15N-labeled proteins provides unique insights into protein backbone motions on the pico- to nanosecond timescale. Nuclear spin relaxation parameters (R1, R2, and heteronuclear {1H}-15N NOE) are routinely measured by well-established multidimensional relaxation experiments, which can be time-consuming typically taking on the order of a week. Recently, NMR chemical exchange saturation transfer (CEST) has emerged as a useful method to probe slow millisecond motions complementing spin relaxation in the rotating frame (R1ρ) and Carr-Purcell-Meiboom-Gill (CPMG) type experiments. CEST also provides site-specific R1 and R2 relaxation parameters requiring only short measurement times of the order of a few hours. We demonstrate that the CEST-derived relaxation parameters accurately reflect relaxation parameters obtained using the traditional method. A “lean” version of the model-free analysis (MFA) is introduced for the interpretation of R1 and R2 resulting in S2 order parameters that closely match those obtained using a standard MFA. The new methodology is demonstrated with experimental data of ubiquitin and arginine kinase and backed up with simulated data derived from microsecond MD simulations of ten different proteins. MD simulations of proteins now routinely extend into the hundreds of nanoseconds time scale range exceeding the overall tumbling correlation times (τc) of proteins in solution. However, presently there is no consensus on how to rigorously validate these simulations by quantitative comparison with model-free order parameters derived from NMR relaxation experiments. For this purpose we conducted MFA of NMR relaxation parameters computed from 500-ns MD trajectories of ten proteins. The resulting model-free S2 order parameters are then used as targets for S2 values co (open full item for complete abstract)

Committee: Rafael Brüschweiler (Advisor); Marcos Sotomayor (Committee Member); Steffen Lindert (Committee Member) Subjects: Biochemistry; Chemistry

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

Polymer-based solar cells (PSCs) require significant improvements in efficiency and life time in order to be commercially viable. Interfacial structure and morphology dictate the performance of PSCs, and these properties in turn depend on processing conditions and surface chemistry. To optimize device performance, detailed knowledge of the factors most critical to the molecular-level structure, morphology and dynamics of donor/acceptor systems at interfaces will be necessary. For one promising donor, poly(3-hexylthiophene (P3HT), we have utilized all-atom and coarse-grained molecular dynamics simulations to investigate such properties at liquid/vacuum, solid/liquid and solid/solid interfaces. At liquid/vacuum interfaces, static and dynamic properties of P3HT films and their dependence on temperature and molecular weight were studied. P3HT chains showed ordering through preferential exposure of side-chain at the interface, and surface tension showed strong dependence on temperature and molecular weight. Properties such as self-diffusion coefficients, chain end-to-end distance and torsion autocorrelations were also utilized to quantify the dynamics of the P3HT chains in the film. Both static and dynamic properties of P3HT were found to be in agreement with well-known models for polymers. Subsequent simulations of P3HT/water systems offered insight into the wetting behavior of P3HT and the nature of the solid-liquid interface in crystalline and amorphous P3HT. From contact angle calculations, different P3HT surfaces were determined to be hydrophobic. In the time scale of our simulations, no observable change in the orientation of the P3HT at interfaces was observed. Furthermore, the molecular ordering of P3HT close to substrates is expected to be the key to device performance. Ordering of P3HT chains at the interface can be tuned by altering the substrate surface chemistry. We investigated the effect of surface chemistry on the ordering of P3HT on self-assemb (open full item for complete abstract)

Committee: Mesfin Tsige Dr. (Advisor); Dhinojwala Ali Dr. (Committee Member); Perry David Dr. (Committee Member); Miyoshi Toshikazu Dr. (Committee Member); Liu Tianbo Dr. (Committee Member) Subjects: Materials Science; Physics; Polymers

MS, University of Cincinnati, 2011, Engineering and Applied Science: Chemical Engineering

The catalytic process of acrylonitrile synthesis from propane known as ammoxidation has recently attracted significant industrial interest due to its environmental advantages and low price of the raw materials. The Mo-V-Te-Nb-O 4-component mixed metal oxide was developed to be the best catalyst for this process. This complex system consists of two distinct phases so-called M1 and M2, which working in synergy make the catalyst to be the most active and selective in the propane ammoxidation reaction. However, the achieved results are not sufficient for the process to be realized commercially on the industrial scale and further improvements of the catalyst performance are required. In order to develop more selective and better performing catalyst it is necessary to attain detailed fundamental understanding of the reaction mechanism which takes place on the surface of the current M1 phase catalyst. It is expected that the best advances in this area can be achieved through the possibilities of the quantum chemistry methods. But these powerful approaches require accurate experimental information on the atomic composition of the studied phases. Meanwhile, due to the analytical difficulties of the available characterization techniques there is luck of experimental data on the exact location of the Nb atoms in the bulk M1 phase 4-component crystal. The location of the Nb atoms in the M1 phase framework is central problem of this research work. The problem was successfully solved using the forcefield-based Molecular Dynamics computational methods. Several force fields were carefully analyzed and the Universal Force Field suitable for the M1 phase description has been chosen to achieve the objectives of this research. Computational studies were conducted using the selected force field for a large number of the Mo-V-O, Mo-V-Te-O and Mo-V-Te-Nb-O M1 phase structures corresponding to various lattice locations of the constituent metal ions in the solid-solution structure of the M (open full item for complete abstract)

Committee: Vadim Guliants PhD (Committee Chair); Vikram Kuppa PhD (Committee Member); Peter Panagiotis Smirniotis PhD (Committee Member) Subjects: Chemistry