Biological and Chemical Physics Commons^™

Predicting Biomolecular Properties And Interactions Using Numerical, Statistical And Machine Learning Methods, Elyssa Sliheet

Mathematics Theses and Dissertations

We investigate machine learning and electrostatic methods to predict biophysical properties of proteins, such as solvation energy and protein ligand binding affinity, for the purpose of drug discovery/development. We focus on the Poisson-Boltzmann model and various high performance computing considerations such as parallelization schemes.

A Causal Inference Approach For Spike Train Interactions, Zach Saccomano

Dissertations, Theses, and Capstone Projects

Since the 1960s, neuroscientists have worked on the problem of estimating synaptic properties, such as connectivity and strength, from simultaneously recorded spike trains. Recent years have seen renewed interest in the problem coinciding with rapid advances in experimental technologies, including an approximate exponential increase in the number of neurons that can be recorded in parallel and perturbation techniques such as optogenetics that can be used to calibrate and validate causal hypotheses about functional connectivity. This thesis presents a mathematical examination of synaptic inference from two perspectives: (1) using in vivo data and biophysical models, we ask in what cases the …

Aspects Of Stochastic Geometric Mechanics In Molecular Biophysics, David Frost

All Dissertations

In confocal single-molecule FRET experiments, the joint distribution of FRET efficiency and donor lifetime distribution can reveal underlying molecular conformational dynamics via deviation from their theoretical Forster relationship. This shift is referred to as a dynamic shift. In this study, we investigate the influence of the free energy landscape in protein conformational dynamics on the dynamic shift by simulation of the associated continuum reaction coordinate Langevin dynamics, yielding a deeper understanding of the dynamic and structural information in the joint FRET efficiency and donor lifetime distribution. We develop novel Langevin models for the dye linker dynamics, including rotational dynamics, based …

Optimization Of Flagellar Locomotion In The Low Reynolds Number Regime, Aidan M. Trodden, Aidan M. Trodden

Physics

This report investigates the computational and theoretical techniques - modeled by E. Lauga and C. Eloy - used to optimize the shape of an activated flagellum for enhanced cell motility. Cell motility is ubiquitous and has a large affect on biological systems such as marine life ecosystems, reproduction, and infection. The physical principles governing flagellar propulsion are explored using computational fluid dynamics simulations, mathematical modeling, and the sequential quadratic programming (SQP) optimization algorithm. Through iterative refinement, we can identify optimized flagellar shapes that would minimize the energetic cost dependent on a single dimensionless sperm numbers (Sp). The computation of the …

Long-Range And Chaotic Active Mixing Of Swimming Microbes In A Vortex Chain Flow, Nghia Le

Honors Theses

We present experiments studying the motion and active mixing of swimming mi- crobes in laminar, vortex-dominated fluid flows. We are testing a theory that predicts the existence of swimming invariant manifolds (SwIMs) - invisible, one-way barriers blocking the paths of self-propelled tracers in the flow in one direction. We also pro- pose that the SwIMs together can form chute structures in three-dimensional phase space that facilitate cross-vortex transport of the microbes. We also observe evidence of how these structures promote long-range transport at different non-dimensional velocities (microbe’s velocity relative to flow velocity). Long-range transport is quan- tified by measuring the …

Inhibitors Of Alpha-Synuclein Aggregation, Jemil Ahmed

Electronic Theses and Dissertations

Alpha-Synuclein (αS) – a neuronal, disordered, presynaptic protein – aggregates into amyloid fibrils and accumulates in the substantia nigra pars compacta of Parkinson's Disease (PD) patients. The aggregation and accumulation of αS amyloid fibrils leads to death of dopaminergic neurons; a hallmark of PD. Although it’s not clear why αS aggregates, prior studies have found that intrastriatal injection of fibril alone is sufficient to cause PD pathology in mouse and non-human primates models. These observations implicate αS as a therapeutic target against PD.

Unfortunately, there are three caveats when attempting to target αS. First, αS is a neuronal protein expressed …

Abhd5 Induced Morphological Changes On Model Membrane Systems, Nasser S. Junedi

Honors College Theses

Proper regulation of neutral lipid storage (lipogenesis) and release (lipolysis) are critical molecular processes localized to an organelle called the Lipid Droplet (LD). The LD consists of a core with neutral lipids such as triacylglycerols (TAGs) and sterol esters surrounded by a phospholipid monolayer. Dysregulation of the processes localized to the LD are involved in the pathology of various diseases such as Neutral Lipid Storage Disease, diabetes, stroke and cancer. The non-enzymatic protein ABHD5 (α-β Hydrolase Domain-Containing Protein 5), is thought to play a key role in the process of lipolysis by forming homo-oligomers on the surface of the LD …

Structure Of Unmodified And Pyroglutamylated Amyloid Beta Peptide In Lipid Membranes, Rowan Hassan

Honors Undergraduate Theses

Alzheimer's Disease (AD) is a devastating neurodegenerative disease that is characterized by brain atrophy, neuronal and synaptic loss, cognitive decline, trouble handling activities of daily life, and ultimately leads to death. Worldwide, at least 30 million people suffer from AD, with 5.8 million suffering in the US alone. Despite extensive basic and clinical research, the underlying molecular mechanisms behind AD remain largely unknown. There are four FDA-approved compounds are used for alleviating symptoms but have no curative potency. The first potentially disease-modifying AD drug, aducanumb, was approved by FDA in June 2021. The main histopathological traits of AD are the …

Structure Difference And Implication To Assembly Morphology Control Of Rous Sarcoma Virus Capsid Protein, John Hastings

Honors Undergraduate Theses

Rous Sarcoma Virus (RSV) is an avian retrovirus with an enclosing capsid protein (CA) shell. RSV CA is studied due to its similar molecular structure to other retrovirus capsid proteins such as Human Immunodeficiency Virus (HIV). In this project, turbidity assay is used to track the assembly process of RSV CA, while solid state nuclear magnetic resonance (ssNMR) is used to probe the CA structure at a site specific level and investigate the morphology of the spherical structure of the I190V mutated strain of RSV CA. The I190V mutant is a naturally occurring mutation and is able to form into …

Equilibrium Partitioning Of Binary Polymer Mixtures Into Biological Nanopores, Mehmet Alphan Aksoyoglu

Doctoral Dissertations

The cell interior, enclosed by membrane barriers, is a condensed solution of inorganic ions, polymers, carbohydrates, polynucleotides, and a large number of other organic molecules. Within cells, transport of metabolites and biopolymers, such as polynucleotides and proteins, occurs partly through specific transmembrane pores (mesoscopic ion channels) spanning cellular compartments. Examples of such functions are translocation of matrix RNA molecules from cell nucleus through nuclear pore complexes, ejection of viral genome from bacterial virus capsids into host bacterial cells, and translocation of protein factors across toxin channels in biological membranes. All these processes, that occur in the cellular milieu, are mediated …

Learning From Disorder And Noise In Physical Biology, Taylor Emil Firman

Electronic Theses and Dissertations

Stochasticity, disorder, and noise play crucial roles in the functioning of many biological systems over many different length scales. On the molecular scale, most proteins are envisioned as pristinely folded structures, but intrinsically disordered proteins (IDPs) have no such folded state and still serve distinct purposes within the cell. At the scale of gene regulation, realistic in vivo conditions produce stochastic fluctuations in gene expression that can lead to advantageous bet-hedging strategies, but can be difficult to characterize using a deterministic framework. Even at the organismal scale, germband extension (GBE) in Drosophila melanogaster embryos systematically elongates the epithelial tissue using …

Characterization Of The Atcc Α-Tc1-6 Pancreatic Alpha Cell Line To Study Glucagon Secretion, Larissa M. Ikenouye

Electronic Theses and Dissertations

The endocrine pancreas is responsible for maintaining glycemic equilibrium in the body. Given the importance of this blood-glucose homeostasis and the implication an unbalance has on Diabetes mellitus, the study of the glucose-sensing alpha and beta cells in the pancreas is a popular field for scientific researchers. In this study, we use immunofluorescence, qPCR analysis, intracellular calcium experiments, and biochemical glucagon secretion assays to determine if the commercially available tumor cell line clone, α-TC1-6 obtained from American Type Culture Collection, is an appropriate model system for glucagon secretion in pancreatic alpha cells. We confirm the production of the hormone peptide …

Cluster Enhanced Nanopore Spectrometry, Amy Chavis

Theses and Dissertations

Nanopore sensing is a label-free method used to characterize water-soluble molecules. Recent work describes how Au₂₅(SG)₁₈ clusters improve the single molecule nanopore spectrometry (SMNS) technique when analyzing polyethylene glycol (PEG). This thesis will further study and optimize the enhancement effect resulting from a cluster’s presence. Additionally, a model describing the interaction between a cluster and PEG is developed to assist in understanding this mechanism of enhancement. This thesis will also discuss expanding the SMNS method to detect peptides, using Au₂₅(SG)₁₈ for enhancement, and adjusting solution conditions to improve the sensitivity of the SMNS system …

Quantumness And Coherence In Photosynthesis, Brian Doolittle

Honors Theses

Long-lived oscillations lasting up to 1800 fs have been observed in the Fenna--Mathews--Olsen (FMO) Pigment-Protein complex. It is unclear if the oscillations are quantum or classical in origin. Quantized intra-pigment normal modes are responsible for these long-lived oscillations. In this thesis we simulate a bacteriachlorophyll dimer in the FMO Complex at physiological conditions. Our model describes two electronically coupled pigments coupled to the vibrational protein environment. Our goal is to find system parameters that allow long-lived quantum coherences to exist in photosynthetic complexes. We calculate the time evolution of our system's density matrix using the numerically exact quantum adiabatic path …

Understanding The Biological And Environmental Implications Of Nanomaterials, Sijie Lin

All Dissertations

The last two decades have witnessed the discovery, development, and large-scale manufacturing of novel nanomaterials. While nanomaterials bring in exciting and extraordinary properties in all areas of materials, electronics, mechanics, and medicine, they also could generate potential adverse effects in biological systems and in the environment. The currently limited application of nanomaterials in biological and ecological systems results from the insufficient and often controversial data on describing the complex behaviors of nanomaterials in living systems. The purpose of this dissertation intends to fill such a knowledge void with methodologies from the disciplines of biophysics, biology, and materials science and engineering. …