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Full-Text Articles in Life Sciences
Amyloid Proteins And Fibrils Stability, Farbod Mahmoudinobar
Amyloid Proteins And Fibrils Stability, Farbod Mahmoudinobar
Dissertations
Compared to globular proteins that have a stable native structure, intrinsically disordered peptides (IDP) sample an ensemble of structures without folding into a native conformation.One example of IDP is the amyloid-beta(Abeta) protein which is the main constituent of senile plaques in the brain of Alzheimer's patients.Understanding the process by which IDPs undergo structural changes to form oligomers that eventually aggregate into senile plaques/amyloid fibrils may significantly advance the development of novel therapeutic methods to treat neurodegenerative diseases, for which there is no cure to date. This dissertation has two main objectives. The first one is to investigate and identify structural …
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 …
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 …
Multiscale Simulations Of Intrinsically Disordered Proteins, Xiaorong Liu
Multiscale Simulations Of Intrinsically Disordered Proteins, Xiaorong Liu
Doctoral Dissertations
Intrinsically disordered proteins (IDPs) lack stable secondary and/or tertiary structures under physiological conditions. The have now been recognized to play important roles in numerous biological processes, particularly cellular signaling and regulation. Mutation of IDPs are frequently associated with human diseases, such as cancers and neuron degenerative diseases. Therefore, it is important to understand the structure, dynamics, and interactions of IDPs, so as to establish the mechanistic basis of how intrinsic disorder mediates versatile functions and how such mechanisms may fail in human diseases. However, the heterogeneous structural ensembles of IDPs are not amenable to high resolution characterization solely through experimental …
Computational Modelling Of Peptides Containing Non-Standard Amino Acids, David W. Kastner
Computational Modelling Of Peptides Containing Non-Standard Amino Acids, David W. Kastner
Undergraduate Honors Theses
Peptides represent a class of abundant and potent pharmaceutic compounds. Despite their appeal, the design, synthesis, and engineering of biologically relevant peptides remain a challenge. Chapter 1 introduces the various computational methods that will be used. Chapter 2 focuses on the incorporation of a special class of amino acids called bulky dehydroamino acids into the turn of β-hairpins to proteolytically stabilize peptides. Our results suggest that dehydroamino acids confer proteolytic stability by favoring a more folded state. Chapter 3 describes the structural calculations of a rare anticancer peptide called Yaku’amide using a combined molecular mechanics/quantum mechanics hybrid method. The …
Impact Of Conformational Change, Solvation Environment, And Post-Translational Modification On Desulfurization Enzyme 2'-Hydroxybiphenyl-2-Sulfinate Desulfinase (Dszb) Stability And Activity, Landon C. Mills
Theses and Dissertations--Chemical and Materials Engineering
Naturally occurring enzymatic pathways enable highly specific, rapid thiophenic sulfur cleavage occurring at ambient temperature and pressure, which may be harnessed for the desulfurization of petroleum-based fuel. One pathway found in bacteria is a four-step catabolic pathway (the 4S pathway) converting dibenzothiophene (DBT), a common crude oil contaminant, into 2-hydroxybiphenyl (HBP) without disrupting the carbon-carbon bonds. 2’-Hydroxybiphenyl-2-sulfinate desulfinase (DszB), the rate-limiting enzyme in the enzyme cascade, is capable of selectively cleaving carbon-sulfur bonds. Accordingly, understanding the molecular mechanisms of DszB activity may enable development of the cascade as industrial biotechnology. Based on crystallographic evidence, we hypothesized that DszB …