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, University of Akron, 2018, Polymer Engineering

The glass transition is a central phenomenon controlling key properties of a wide variety of materials, ranging from polymers, organic and inorganic molecules to metals. Derived applications can be found in solar storage panels, global communications, tires, consumer electronics and so forth. Despite two centuries of dedicated research attempting to elucidate the fundamental mechanisms, no consensus on how a glass is formed is reached. Molecular dynamics (MD) simulation has been used as a powerful conduit for probing the nanoscale dynamics and has contributed significantly to the modern understanding of the glass transition, which by nature is a nanoscale problem where the decisive local structural relaxation spans from 1-10 nm. However, supercooled simulations in the past 30 years have shown an inability to probe the local relaxation time, ta, longer than 100 ns on most commercially available hardware. This limitation has posed serious threats to a full-fledged understanding of the glass transition and to the ability of simulation to quantitatively predict the glass transition measured at the laboratorial timescale, which by convention is defined at 100 s. In this work, we develop a bootstrapping quench-anneal approach for efficient supercooled simulation which collects well equilibrated data. This algorithm is named Predictive Stepwise Quenching (PreSQ) and has been integrated into a fully automated workflow. PreSQ demonstrates superior data reproducibility and offers at least 100-fold enhancement in efficiency over any existing protocols for supercooled simulation. PreSQ enables key insights into the underlying mechanisms of glass formation. The precipitous dynamic arrest that causes the glass transition has long been linked to the underlying particle localization. Through PreSQ, an unprecedented supercooled data covering more than 50 chemistries and 3000 data points, spanning 7+ decades of relaxation timescale, has been generated. From this remarkable data (open full item for complete abstract)

Committee: David Simmons (Advisor); Kevin Cavicchi (Committee Chair); Bryan Vogt (Committee Member); Mesfin Tsige (Committee Member); Malena Espanol (Committee Member) Subjects: Physics; Polymers

Doctor of Philosophy, The Ohio State University, 2011, Pharmacy

The objective of this dissertation was to design small molecule drug candidates for different disease targets by understanding the energetics and dynamics of their binding protein/enzyme/receptor partners. Protein-protein interactions are intrinsic to virtually every cellular process such as transcription regulation and signal transduction, and inappropriate protein-protein interactions may lead to human diseases such as cancer. These interactions commonly rely on a few key residues (“hot spot residues”) and single point mutations of “hot spot” residues could cause disruption of theses protein complexes. Hence, small molecule antagonists, which interfere mainly with critical amino acid contacts, could have significant outcomes on disruption of binding equilibrium of protein/protein complex. By utilizing this concept, we have designed IL-6 inhibitors to disrupt interactions between IL-6 and gp130 (chapter 2, 3 and 4). Traditional drug discovery begins by identifying the protein target related to disease and finding a lead compound, a potential drug that bears the desired physical and biological features from a library of known chemical compounds. This limits the search space from the beginning and makes new drug discovery (new chemical structure) a very difficult task. However, as the cellular and molecular mechanisms behind many diseases are increasingly understood, new avenues for rational drug development emerge. This can be complemented by structure based drug design methods that utilize three dimensional structure of the target protein. Recent advancements in computational techniques and hardware have helped researchers using in silico methods to a speedy lead identification and optimization. Large virtual chemical libraries are now available for screenings that lead to discovery of small molecule inhibitors of HIV-IN and LEDGF interactions (Chapter 5 and 6). Protein/receptor structures are not static in the body; they often bear plasticity by accommodating ch (open full item for complete abstract)

Committee: Chenglong Li (Advisor); James Fuchs R (Committee Member); Jiayuh Lin (Committee Member) Subjects: Bioinformatics; Biophysics; Pharmacy Sciences

PHD, Kent State University, 2007, College of Arts and Sciences / Department of Physics

A Langmuir film is a molecularly thin layer self confined at a liquid/vapor interface (typically air/water). We studied Langmuir layer of bent-core molecules which have bent cores with phenyl rings and two long and flexible end-chains. Due to their special molecular structure, bent-core molecules exhibit a rich variety of phases, including many liquid crystalline ones. A dozen different liquid phases and five smectic phases have been suggested. At least eight phases have been identified, but most have not been fully characterized. The usefulness of bent-core molecules in all kinds of devices has been demonstrated. Studies of growth mechanism, molecular ordering, and the overall film morphology are of prime importance for device design. The Langmuir layer can give insight into the molecular packing within layers, particularly in the presence of an interface. For bulk liquid crystal, the order at this interface can help in understand the order in bulk. Bent-core molecules that show smectic ordering, even if only at higher temperatures, may be expected to form reversible collapsed layers. A stable Langmuir layer, transferred to a solid interface, may form a natural alignment layer for bent-core liquid crystals. It has been very difficult to align bent-core molecules, and many of the zero-field characteristics have had to be deduced from quite inhomogeneous films. Studies of Langmuir layers may thus help clear up structural questions about bent-core liquid crystals in two ways: directly, by what can be deduced from the structure of the Langmuir layers themselves, and indirectly, through the possibility of providing a suitable alignment layer to produce more homogeneous, thicker films. My work concentrated on two kinds of bent-core molecules: One with siloxane end-chains and the other with hydrocarbon end-chains. Both the bent-cores and end-chains will be varied. Systematic study will be carried on some particular molecule. The experimental methods includes: Surface Pres (open full item for complete abstract)

Committee: Elizabeth Mann (Advisor) Subjects: