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Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel
Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel
Honors Scholar Theses
Among structural biology techniques, Nuclear Magnetic Resonance (NMR) provides a holistic view of structure that is close to protein structure in situ. Namely, NMR imaging allows for the solution state of the protein to be observed, derived from Nuclear Overhauser Effect restraints (NOEs). NOEs are a distance range in which hydrogen pairs are observed to stay within range of, and therefore experimental data which computational models can be compared against. To that end, we investigated the effects of adding the NOE restraints as distance restraints in Molecular Dynamics (MD) simulations on the 24 residue HP24stab derived villin headpiece subdomain to …
Computational Investigations Into Binding Dynamics Of Tau Protein Antibodies: Using Machine Learning And Biophysical Models To Build A Better Reality, Katherine Lee
University Scholar Projects
Misregulation of post-translational modifications of microtubule-associated protein tau is implicated in several neurodegenerative diseases including Alzheimer’s disease. Hyperphosphorylation of tau promotes aggregation of tau monomers into filaments which are common in tau-associated pathologies. Therefore, tau is a promising target for therapeutics and diagnostics. Recently, high-affinity, high-specificity single-chain variable fragment (scFv) antibodies against pThr-231 tau were generated and the most promising variant (scFv 3.24) displayed 20-fold increased binding affinity to pThr-231 tau compared to the wild-type. The scFv 3.24 variant contained five point mutations, and intriguingly none were in the tau binding site. The increased affinity was hypothesized to occur due …
Molecular Simulation Study Of Protein Conformation Change, Binding Mechanisms, And Allosteric Communication, Jason Pattis
Molecular Simulation Study Of Protein Conformation Change, Binding Mechanisms, And Allosteric Communication, Jason Pattis
Doctoral Dissertations
Many processes in biology involve conformational changes or binding events which can be described by a pathway or ensemble of pathways. These processes are challenging to study experimentally as obtaining the temporal and spatial resolution sufficient to understand the underlying physical mechanisms can be challenging. Molecular dynamics (MD) simulations is a powerful tool that can provide atomic resolution on these processes and aid in the design and interpretation of experiments. In this thesis, I will describe MD simulations using enhanced sampling methods to investigate several biomolecular systems, including the Lassa virus nucleoprotein, phosphodiesterase enzymes and a peptide from the Flock …
Computational Analysis Of Poliovirus Structural Dynamics Using A Coarse-Grained Model, Maneesh Koneru
Computational Analysis Of Poliovirus Structural Dynamics Using A Coarse-Grained Model, Maneesh Koneru
University Scholar Projects
Though eradicated in most of the world, poliovirus remains a common model virus for a family of mammalian viruses known as Picornaviruses. Despite the development of a vaccination, little is understood about the infection process, particularly the mechanism of cell entry. Experimental studies have attempted to elucidate the dynamics of this process and have proposed pathways focused on VP4, the smallest of the four peptides which makes up the viral capsid, and its interaction with the pentameric interfaces of the five fold axes. This study utilizes coarse-grained molecular dynamics to supplement these proposed mechanisms with simplified simulations which reduce the …
Diffusion On Silver Nanorod Surfaces: Mechanisms Of Fast Diffusion At Low Temperature, Lou Bachenheimer
Diffusion On Silver Nanorod Surfaces: Mechanisms Of Fast Diffusion At Low Temperature, Lou Bachenheimer
Doctoral Dissertations
Ag nanorods may serve as sensors in the detection of trace amounts of chemical agents, even single molecules, through surface enhanced Raman spectroscopy (SERS). However, thermal coarsening of Ag nanorods near room temperature limits their applications. In this work, we examine this thermal instability through molecular dynamics simulations and molecular statics calculations in order to elucidate the process. From these computational methods, it is realized that the thermal instability of Ag nanorods is the result of rapid surface diffusion, and we hypothesize that the thermal stability can be enhanced by the addition of a thin dielectric cap. This hypothesis is …
Stability Of Norwalk Virus Capsid Protein Interfaces Evaluated By In Silico Nanoindentation, Prakhar Bansal
Stability Of Norwalk Virus Capsid Protein Interfaces Evaluated By In Silico Nanoindentation, Prakhar Bansal
University Scholar Projects
Studying the mechanical properties of viral capsids can give several insights into not only the lifecycle of the virus, but also into potential drug targets to thwart the progression of viral infection. Nanoindentation using an atomic force microscope is a useful technique for determining structural properties of small molecules and particles, and is commonly used to study viral capsids. This technique utilizes the probe of the microscope to push down on the capsid and record the forces along the indentation path. We ran this experiment in silico where we simulated the nanoindentation of Norwalk virus capsids using molecular dynamics. Running …
Computational Investigations Into The Molecular Underpinnings Of Eyesight Signaling Pathways, Shaan Kamal
Computational Investigations Into The Molecular Underpinnings Of Eyesight Signaling Pathways, Shaan Kamal
University Scholar Projects
Phosphodiesterase 6 (PDE6) is a critical enzyme in the eyesight-signaling pathway. When activated, PDE6 hydrolyzes cGMP to GMP, which deactivates cGMP- gated ion channels, causing hyperpolarization of the cell and activating the sensory neurons responsible for vision. Within the PDE family, PDE6 is the only enzyme known to have an inhibitory subunit (PDE6-γ), which allows for the regulation of cGMP levels. When PDE6-γ is bound to PDE6, the enzyme is turned “off” and cannot catalyze cGMP. The α subunit of the G-protein transducin removes PDE6-γ and activates PDE6. PDE6 has proven problematic to isolate, making it difficult to study experimentally …
Implementation And Application Of The Response Eam For Hcp Metals, Matthew J. Stagon
Implementation And Application Of The Response Eam For Hcp Metals, Matthew J. Stagon
Master's Theses
Atomistic simulations are a powerful tool for the study of materials, especially in the determination of underlying atomistic mechanisms. Molecular dynamics (MD) is an atomistic simulation method that is well suited for a large number of atoms in a system, up to one billion. MD holds sufficient physical rigor while keeping the number of calculations reasonable for modern computational power. In molecular dynamics, a mathematical potential is used to capture the physics of the interaction between two adjacent atoms or molecules. Existing potentials fail to adequately represent the interaction between some materials, such as Magnesium and Titanium, or are based …
Agent-Based Modeling Of Emergency Building Evacuation, Vi Q. Ha
Agent-Based Modeling Of Emergency Building Evacuation, Vi Q. Ha
Master's Theses
Panic during emergency building evacuation can cause crowd stampede, resulting in serious injuries and casualties. Agent-based methods have been successfully employed to investigate the collective human behavior during emergency evacuation in cases where the configurational space is extremely simple - usually one rectangular room - but not in evacuations of multi-room or multi-floor buildings. This implies that the effect of the complexity of building architecture on the collective behavior of the agents during evacuation has not been fully investigated. Here, we employ a system of self-moving particles whose motion is governed by the social-force model to investigate the effect of …