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Articles 1 - 10 of 10
Full-Text Articles in Physical Sciences and Mathematics
Computational Methods For Analysis Of Data For Conformational And Phase Equilibria Of Disordered Proteins, Jared Michael M Lalmansingh
Computational Methods For Analysis Of Data For Conformational And Phase Equilibria Of Disordered Proteins, Jared Michael M Lalmansingh
Arts & Sciences Electronic Theses and Dissertations
Intrinsically disordered proteins and regions (IDPs / IDRs) are a class of proteins with diverse conformational heterogeneity that do not fold into a tertiary structure due to the lack of a native structural state. Consequently, disordered proteins are remarkably flexible and exhibit multivalent properties that enable them to adopt myriad functional roles within the cell such as: signaling transduction, transcription, enzymatic catalysis, translation, and many more. Due to their multivalency, some IDPs undergo monomeric and heterotypic interactions which can drive phase separation. Such IDPs can form membraneless organelles with specific regulatory roles within the cell which include, but are not …
Specificity Of Ssb Binding To Its Interacting Proteins And Multiple Allosteric Effects Of Ssb C-Terminal Tail On Assembly And Dna Binding Of E. Coli Recor Proteins, Min Kyung Shinn
Arts & Sciences Electronic Theses and Dissertations
The homo-tetrameric E. coli single strand (ss) DNA binding (SSB) protein is an essential component in DNA maintenance for its role in binding and protecting single stranded DNA intermediates via its N-terminal DNA binding domain (DBD). SSB also acts as a hub to recruit at least 17 SSB interacting proteins (SIPs) involved in DNA replication, recombination, and repair via its 9 amino acid C-terminal acidic tip region. A 56 amino acid intrinsically disordered linker connects the DBD and the acidic tip and plays a role in cooperative binding to ssDNA. Using isothermal titration calorimetry, I determined that the SSB-Ct peptides …
Phantoms To Placentas: Mr Methods For Oxygen Quantification, Kelsey Meinerz
Phantoms To Placentas: Mr Methods For Oxygen Quantification, Kelsey Meinerz
Arts & Sciences Electronic Theses and Dissertations
Molecular oxygen (O2) is vital for efficient energy production and improper oxygenation is a hallmark of disease or metabolic dysfunction. In many pathologies, knowledge of tissue oxygen levels (pO2) could aid in diagnosis and treatment planning. The gold standard for pO2 measures in tissue are implantable probes, which are invasive, require surgery for placement, and are inaccessible to certain regions of the body. Methods for determining pO2 both non-invasively and quantitatively are lacking. The slight paramagnetic nature of O2 provides opportunities to non-invasively characterize pO2 in tissue via magnetic resonance (MR) techniques. As such, O2 can be treated as a …
Development And Application Of Mass Spectrometry-Based Protein Footprinting In Structural Proteomics, Ming Cheng
Development And Application Of Mass Spectrometry-Based Protein Footprinting In Structural Proteomics, Ming Cheng
Arts & Sciences Electronic Theses and Dissertations
Integral mass spectrometry (MS) has emerged as an important tool for protein structural characterization. It readouts are a broad range of structural information, including stoichiometry, interactions, conformations and conformation change, and dynamics. Protein footprinting is a pivotal component in the intergral MS toolkit.My dissertation centers around the development and application of protein footprinting to characterize protein structure. It is divided into seven chapters.Chapter 1 serves as the introduction for integral mass spectrometry in structural proteomic.In Chapter 2, we extended the fast-photochemical oxidation of proteins (FPOP) platform by adding the trifluoromethyl radical (•CF3) as a new reagent. We discovered that •CF3 …
A Physics-Based Intermolecular Potential For Biomolecular Simulation, Joshua Andrew Rackers
A Physics-Based Intermolecular Potential For Biomolecular Simulation, Joshua Andrew Rackers
Arts & Sciences Electronic Theses and Dissertations
The grand challenge of biophysics is to use the fundamental laws of physics to predict how biological molecules will move and interact. The atomistic HIPPO (Hydrogen-like Intermolecular Polarizable Potential) force field is meant to address this challenge. It does so by breaking down the intermolecular potential energy function of biomolecular interactions into physically meaningful components (electrostatics, polarization, dispersion, and exchangerepulsion) and using this function to drive molecular dynamics simulations. This force field is able to achieve accuracy within 1 kcal/mol for each component when compared with ab initio Symmetry Adapted Perturbation Theory calculations. HIPPO is capable of this accuracy because …
Fast-Forward Protein Folding And Design: Development, Analysis, And Applications Of The Fast Sampling Algorithm, Maxwell Isaac Zimmerman
Fast-Forward Protein Folding And Design: Development, Analysis, And Applications Of The Fast Sampling Algorithm, Maxwell Isaac Zimmerman
Arts & Sciences Electronic Theses and Dissertations
Molecular dynamics simulations are a powerful tool to explore conformational landscapes, though limitations in computational hardware commonly thwart observation of biologically relevant events. Since highly specialized or massively parallelized distributed supercomputers are not available to most scientists, there is a strong need for methods that can access long timescale phenomena using commodity hardware. In this thesis, I present the goal-oriented sampling method, Fluctuation Amplification of Specific Traits (FAST), that takes advantage of Markov state models (MSMs) to adaptively explore conformational space using equilibrium-based simulations. This method follows gradients in conformational space to quickly explore relevant conformational transitions with orders of …
Sequence Determinants Of The Individual And Collective Behaviour Of Intrinsically Disordered Proteins, Alexander S. Holehouse
Sequence Determinants Of The Individual And Collective Behaviour Of Intrinsically Disordered Proteins, Alexander S. Holehouse
Arts & Sciences Electronic Theses and Dissertations
Intrinsically disordered proteins and protein regions (IDPs) represent around thirty percent of the eukaryotic proteome. IDPs do not fold into a set three dimensional structure, but instead exist in an ensemble of inter-converting states. Despite being disordered, IDPs are decidedly not random; well-defined - albeit transient - local and long-range interactions give rise to an ensemble with distinct statistical biases over many length-scales. Among a variety of cellular roles, IDPs drive and modulate the formation of phase separated intracellular condensates, non-stoichiometric assemblies of protein and nucleic acid that serve many functions. In this work, we have explored how the amino …
Determining The Molecular Mechanisms Of Huntington’S Disease Through Multi-Scale Modeling, Kiersten Ruff
Determining The Molecular Mechanisms Of Huntington’S Disease Through Multi-Scale Modeling, Kiersten Ruff
Arts & Sciences Electronic Theses and Dissertations
Huntington’s disease (HD) is associated with a mutational CAG repeat expansion within exon 1 of the huntingtin (Htt) gene. Post-transcriptional processing leads to the generation of N-terminal Htt protein fragments (Htt-NTFs), including those that encompass exon 1 (Httex1). Within Httex1, the CAG-repeat encoded polyglutamine (polyQ) tract is flanked N-terminally by a 17-residue amphipathic stretch (N17) and C-terminally by a 50-residue proline rich (PR) domain. Htt-NTFs, including Httex1, are among the smallest fragments that recapitulate HD pathology in mouse models. However, the direct link between Htt-NTFs with polyQ expansions and neurodegeneration that leads to HD remains unresolved. Despite being a monogenic …
Disordered Proteins: Connecting Sequences To Emergent Properties, Tyler Scott Harmon
Disordered Proteins: Connecting Sequences To Emergent Properties, Tyler Scott Harmon
Arts & Sciences Electronic Theses and Dissertations
Many IDPs participate in coupled folding and binding reactions and form alpha helical structures in their bound complexes. Alanine, glycine, or proline scanning mutagenesis approaches are often used to dissect the contributions of intrinsic helicities to coupled folding and binding. These experiments can yield confounding results because the mutagenesis strategy changes the amino acid compositions of IDPs. Therefore, an important next step in mutagenesis-based approaches to mechanistic studies of coupled folding and binding is the design of sequences that satisfy three major constraints. These are (i) achieving a target intrinsic alpha helicity profile; (ii) fixing the positions of residues corresponding …
Actin-Based Feedback Circuits In Cell Migration And Endocytosis, Xinxin Wang
Actin-Based Feedback Circuits In Cell Migration And Endocytosis, Xinxin Wang
Arts & Sciences Electronic Theses and Dissertations
In this thesis, we study the switch and pulse functions of actin during two important cellular processes, cell migration and endocytosis. Actin is an abundant protein that can polymerize to form a dendritic network. The actin network can exert force to push or bend the cell membrane. During cell migration, the actin network behaves like a switch, assembling mostly at one end or at the other end. The end with the majority of the actin network is the leading edge, following which the cell can persistently move in the same direction. The other end, with the minority of the actin …