Molecular Biology Commons^™

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …

Modulation Of Protein Dynamics By Ligand Binding And Solvent Composition, Richard J. Lindsay

Doctoral Dissertations

Many proteins undergo conformational switching in order to perform their cellular functions. A multitude of factors may shift the energy landscape and alter protein dynamics with varying effects on the conformations they explore. We apply atomistic molecular dynamics simulations to a variety of biomolecular systems in order to investigate how factors such as pressure, the chemical environment, and ligand binding at distant binding pockets affect the structure and dynamics of these protein systems. Further, we examine how such changes should be characterized. We first investigate how pressure and solvent modulate ligand access to the active site of a bacterial lipase …

Exploring Structure-Dynamics-Function Relationship In Proteins, Protein: Ligand And Protein: Protein Systems Through Computational Methods, Karan Pal Kapoor

Doctoral Dissertations

The study focuses on understanding the dynamic nature of interactions between molecules and macromolecules. Molecular modeling and simulation technologies are employed to understand how the chemical constitution of the protein, specific interactions and dynamics of its structure provide the basis of its mechanism of function. The structure-dynamics-function relationship is investigated from quantum to macromolecular-assembly level, with applications in the field of rationale drug discovery and in improving efficiency of renewable sources of energy. Results presented include investigating the role of dynamics in the following:

1) In interactions between molecules: analyzing dynamic nature of a specific non-covalent interaction known as “anion-π …

Pore Selectivity And Gating Of Arabidopsis Nodulin 26 Intrinsic Proteins And Roles In Boric Acid Transport In Reproductive Growth, Tian Li

Doctoral Dissertations

Plant nodulin-26 intrinsic proteins (NIPs) are members of the aquaporin superfamily that serve as multifunctional channels of uncharged metabolites and water. They share the same canonical hourglass fold as the aquaporin family. The aromatic arginine (ar/R) selectivity filter controls transport selectivity based on size, hydrophobicity, and hydrogen bonding with substrates. In Arabidopsis thaliana, NIP II subclass proteins contain a conserved ar/R “pore signature” that is composed of Alanine at the helix 2 position (H2), Valine/Isoleucine at the helix 5 position (H5), and an Alanine (LE1) and an invariant Arginine (LE2) at the two loop E positions. In this study, …

Applications And Improvements In The Molecular Modeling Of Protein And Ligand Interactions, Jason Bret Harris

Doctoral Dissertations

Understanding protein and ligand interactions is fundamental to treat disease and avoid toxicity in biological organisms. Molecular modeling is a helpful but imperfect tool used in computer-aided toxicology and drug discovery. In this work, molecular docking and structural informatics have been integrated with other modeling methods and physical experiments to better understand and improve predictions for protein and ligand interactions. Results presented as part of this research include:

1.) an application of single-protein docking for an intermediate state structure, specifically, modeling an intermediate state structure of alpha-1-antitrypsin and using the resulting model to virtually screen for chemical inhibitors that can …

Application Of Computational Molecular Biophysics To Problems In Bacterial Chemotaxis, Davi Ortega

Doctoral Dissertations

The combination of physics, biology, chemistry, and computer science constitutes the promising field of computational molecular biophysics. This field studies the molecular properties of DNA, protein lipids and biomolecules using computational methods. For this dissertation, I approached four problems involving the chemotaxis pathway, the set of proteins that function as the navigation system of bacteria and lower eukaryotes.

In the first chapter, I used a special-purpose machine for molecular dynamics simulations, Anton, to simulate the signaling domain of the chemoreceptor in different signaling states for a total of 6 microseconds. Among other findings, this study provides enough evidence to propose …

Soybean Nodulin 26: A Channel For Water And Ammonia At The Symbiotic Interface Of Legumes And Nitrogen-Fixing Rhizobia Bacteria, Jin Ha Hwang

Doctoral Dissertations

During the infection and nodulation of legume roots by soil bacteria of the Rhizobiaceae family, the invading endosymbiont becomes enclosed within a specialized nitrogen-fixing organelle known as the "symbiosome". In mature nodules the host infected cells are occupied by thousands of symbiosomes, which constitute the major organelle within this specialized cell type. The symbiosome membrane is the outer boundary of this organelle which controls the transport of metabolites between the symbiont and the plant host. These transport activities include the efflux of the primary metabolic product of nitrogen fixation and the uptake of dicarboxylates as an energy source to support …

Investigating The Flexibility Of Intrinsically Disordered Proteins In Folding And Binding, Amanda Leilah Debuhr

Chancellor’s Honors Program Projects

No abstract provided.

A Time-And-Space Parallelized Algorithm For The Cable Equation, Chuan Li

Doctoral Dissertations

Electrical propagation in excitable tissue, such as nerve fibers and heart muscle, is described by a nonlinear diffusion-reaction parabolic partial differential equation for the transmembrane voltage $V(x,t)$, known as the cable equation. This equation involves a highly nonlinear source term, representing the total ionic current across the membrane, governed by a Hodgkin-Huxley type ionic model, and requires the solution of a system of ordinary differential equations. Thus, the model consists of a PDE (in 1-, 2- or 3-dimensions) coupled to a system of ODEs, and it is very expensive to solve, especially in 2 and 3 dimensions.

In order to …

Dynamics Of The Toc Gtpases: Modulation By Nucleotides And Transit Peptides Reveal A Mechanism For Chloroplast Protein Import, Lovett Evan Reddick

Doctoral Dissertations

The chloroplast is the green organelle in the plant cell responsible for harvesting energy from sunlight and converting it into sugars and ATP. Origins of this organelle can be traced back to an endosymbiotic event in which a primitive eukaryotic cell capable of oxidative phosphorylation engulfed a free-living cyanobacterium capable of photosynthetic respiration (1). Immediately following this event the details are not clear, however what is known is that over the course of evolution, the engulfed cyanobacteria relinquished approximately 97% of its protein coding sequences to the host cell nucleus, thus making the newly formed chloroplast reliant on its host …