Physical Sciences and Mathematics Commons^™

Using Qm/Mm Methods To Explore Sortase Enzyme Intermediates, Kinetics, And Stability, Kyle Whitham

WWU Graduate School Collection

Biochemistry has seen advancements in methods and understanding of the inner workings of proteins, yet biochemists struggle to see real time reaction pathways of protein intermediates. This is where computational chemistry comes in and fills in the holes in knowledge through the use of Quantum Mechanical (QM) models. QM chemistry alone does not give results in a reasonable timescale to predict protein chemistry in a reasonable amount of time. Computational chemistry methods such as Quantum mechanical (QM)/ Molecular Mechanical (MM) (QM/MM), allow us to split the in-silico system into two regions that utilize a fast MM force field region and …

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

Stability, Electronic Structure, And Nonlinear Optical Properties In Clusters And Materials: A Synergistic Experimental-Computational Analysis, Maksim Kulichenko

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The main objective of Chemistry as a science is an understanding of how and why certain atoms are bonded together and what effects these bonds cause. Modern computational chemistry offers a wide range of tools that greatly assist the exploration of vast chemical space replacing expensive trial-and-error experimental approaches. Computational chemistry may serve to characterize newly synthesized compounds and provide atomic scale insights inaccessible to experimentalists’ vision. Moreover, predictive power of computational chemistry may be used as a guidance for future experiments and for the rational design of new compounds with desired properties.

This dissertation demonstrates the capabilities of joint …

Relative Energy Comparison For Various Water Clusters Using Mp2, Df-Mp2, And Ccsd(T):Mp2 Methods, Qihang Wang

Honors Theses

The study of water clusters is an important area of research in many disciplines, such as biology, physical chemistry, and environmental studies. However, due to the difficulty in studying larger water clusters, such as clathrate hydrates, it is beneficial to obtain accurate descriptions of smaller water clusters to use as models for larger systems via computational methods. By starting with small water clusters, such as (H2O)₆, and moving into larger systems it is possible to build up data on various water structures that can determine the energetics of the various geometries within a certain number of water molecules. …

Understanding The Proton Transport In Non-Aqueous Histidine-Based Nanostructures, Jiang Bian

Dissertations, Theses, and Capstone Projects

Over the past two decades, proton transport has been extensively studied because of the many applications to the development of new technological devices. In particular, understanding proton transport permits the design of new materials with desired properties for constructing effective proton exchange membranes (PEM) in fuel cells. Current PEM technology involves biocummulative perfluorinated membranes that operate under hydrated conditions, for which the proton conductivity is limited by the usually high temperature that fuel cells operate. Therefore, it is of great interest to study the alternative systems that have the potential to conduct protons, in particular, those that are able to …

Quantum Mechanics-Based Computational Chemistry Has Become A Powerful Partner In The Scientific Research Of Nitrogen-Rich Compounds, Paving The Way For Important Advances In Biochemical, Pharmacological And Other Related Fields, Dobrushe Denburg

Student Theses and Dissertations

The Computational Chemistry of Nitrogen-Rich Compounds; Insight into Pioneering Research

Nitrogen-rich functional groups have long been studied for their diversity; nitrogen can form single, double and triple bonds with itself, and will therefore exist in a very broad range of molecular arrangements. Poly-nitrogen compounds are highly energetic and electron rich, and many compounds display unique properties that allow participation in very specialized chemical reactions. Of import is their ubiquity in biological systems, and throughout the past century and currently, their biological relevance is deeply and widely explored in biochemistry and biomedicine, from their involvement in natural biological processes and complex …

Suzuki Coupling Catalyzed By (8-(Dimesitylboryl)Quinoline)Palladium(0) Species: A Theoretical Analysis, Haley S. Rust

Honors Thesis

The Suzuki reaction is a catalyzed cross-coupling reaction which is of upmost importance in the formation of carbon-carbon (C-C) bonds in modern organic synthesis. Recently a new catalyst including an 8-(dimesitylboryl)quinoline for the coupling of aryl halides with phenylboronic acids was synthetized. We synthesized ligand that includes a frustrated Lewis pair, (quinolin-8-yl)dimesitylborane (DMBQ), complexed it with group X metals (nickel (Ni), palladium (Pd), and platinum (Pt)), and studied the process of oxidative addition with carbon-fluorine (C-F) bonds and activation towards Suzuki coupling. Mayer bond analysis and electron localization function maps showed a bond between the boron center in the ligand …

Computational Insights On Medicinal Chemistry Targeting Cyp450s, Alexander D. Fenton

Theses and Dissertations--Chemistry

Modern-day medicinal chemistry has provided researchers with a wide variety of tools to not only gather greater insight from their data, but also to generate data in new ways. One such tool is the construction of computational protein models from crystallographic datasets, and their subsequent use to understand the structure-activity relationships of protein-ligand complexes. These models can be utilized for their predictive power to inform the synthesis of, and improvement of, lead compounds. It is the goal of this work to employ such models to the CYP450 enzyme system such that potent and selective inhibitors can be designed, evaluated biologically, …

Effect Of Charged Lipids On The Ionization Behavior Of Glutamic Acid Containing Transmembrane Helices, Brooke Nunn

Chemistry & Biochemistry Undergraduate Honors Theses

Transmembrane proteins make up critical components of living cells. Protein function can be greatly impacted by the charged state of its respective components, the side chains of amino acid residues. Thus far, in the lipid membrane, little is known about the properties of residues such as glutamic acid. To explore these properties, I have included glutamic acid in a suitable model peptide-lipid system for fundamental biophysical experiments. Within the system, I have placed a glutamic acid residue instead of leucine in the L14 position of the helical hydrophobic peptide GWALP23 (acetyl-GGALWLALALALAL¹⁴ALALWLAGA-amide). Substitutions of glutamine and aspartic acid serve …

Raman Spectroscopic And Quantum Chemical Investigation Of The Effects Of Tri-Methylamine N-Oxide (Tmao) On Hydrated Urea, Hydrated Guanidinium, And Hydrogen Bonded Networks, Genevieve Verville

Honors Theses

Trimethylamine N-Oxide (TMAO), guanidinium, and urea are three important

osmolytes with their main significance to the biophysical field being in how they

uniquely interact with proteins. TMAO is known to stabilize and counteract the

destabilizing effects of both urea and guanidinium. The exact mechanisms by which

TMAO stabilizes and both guanidinium and urea destabilize folded proteins continue

to be debated in the literature. Some studies suggest that solvent interactions do not

play a large role in TMAO’s stabilizing effects and therefore advocate direct

stabilization, whereas others suggest that TMAO counteracts denaturation primarily

through an indirect effect of strong solvent interactions. …

Electronic Transmutation: An Aid For The Rational Design Of New Chemical Materials Using The Knowledge Of Bonding And Structure Of Neighboring Elements, Katie A. Lundell

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Everything in the universe is made up of elements from the periodic table. Each element has its own role that it plays in the formation of things it makes up. For instance, pencil lead is graphite. A series of honeycomb-like structures made up of carbon stacked on top of one another. Carbon’s neighbor to the left, boron doesn’t like to form such stacked honeycomb-like structures. But, what if there was a way to make boron act like carbon so it did like to form such structures? That question is the basis of the electronic transmutation concept presented in this dissertation. …

Modeling The Condensed-Phase Behavior Of Π-Conjugated Polymers, Walker Mask

Theses and Dissertations--Chemistry

It is well established that the morphology and physical properties of an organic semiconducting (OSC) material regulate its electronic properties. However, structure-function relationships remain difficult to describe in polymer-based OSC, which are of particular interest due to their robust mechanical properties. If relationships among the molecular and bulk levels of structure can be found, they can aid in the design of improved materials. To explore and detail important structure-function relationships in polymer-based OSC, this work employs molecular dynamics (MD) simulations to study various π-conjugated polymers in different environments. Two independent investigations are discussed in this work. One investigation examines how …

Gas-Surface Interactions: Reactive And Non-Reactive Scattering, Azar Farjamnia

Doctoral Dissertations

The adsorption and dissociation of small molecules on metal surfaces are key steps in many industrial reactions. A detailed understanding of the dynamics of these reactions provides us with the ability to control the outcome and efficacy of the reactions. The molecule-metal interactions will lead to reorientation, energy redistribution, or bond dissociation in the molecule. The process is strongly depending upon the initial conditions, i. e. the incident energy and vibrational state of the molecule, and the surface temperature. We use a fully quantum approach to compute the dissociative sticking probability of the molecules at zero overage, on the surface …

Quantum Roaming Dynamics On Model Double Morse And Ion-Molecule Potentials, Luke O'Connor

HON499 projects

The quantum dynamics on a pair of model two dimensional potential energy surfaces is studied using time-independent and wave packet analyses. The first potential is a reduced dimensional model of an ion-dipole reaction and the second is a planar double Morse potential. Both potentials have been of recent interest in characterizing the roaming reaction mechanism using classical dynamics. Roaming resonance states related to the classically observed roaming dynamics are isolated, and quantum signatures of roaming on these potentials are discussed. The effects of the shape of the double Morse potential on the quantum dynamics are also considered.

Computational Optimization And Characterization Of Molecularly Imprinted Polymers, Jacob Jordan Terracina

Legacy Theses & Dissertations (2009 - 2024)

Molecularly imprinted polymers (MIPs) are a class of materials containing sites capable of selectively binding to the imprinted target molecule. Computational chemistry techniques were used to study the effect of different fabrication parameters (the monomer-to-target ratios, pre-polymerization solvent, temperature, and pH) on the formation of the MIP binding sites. Imprinted binding sites were built in silico for the purposes of better characterizing the receptor – ligand interactions. Chiefly, the sites were characterized with respect to their selectivities and the heterogeneity between sites.

Experimental Methods In Cryogenic Spectroscopy: Stark Effect Measurements In Substituted Myoglobin, Bradley Michael Moran

Theses and Dissertations

Dawning from well-defined tertiary structure, the active regions of enzymatic proteins exist as specifically tailored electrostatic microenvironments capable of facilitating chemical interaction. The specific influence these charge distributions have on ligand binding dynamics, and their impact on specificity, reactivity, and biological functionality, have yet to be fully understood. A quantitative determination of these intrinsic fields would offer insight towards the mechanistic aspects of protein functionality. This work seeks to investigate the internal molecular electric fields that are present at the oxygen binding site of myoglobin.

Experiments are performed at 1 K on samples located within a glassy matrix, using the …

Mining Uranium From Seawater: A Coordination Chemistry Approach, Nada Mehio

Doctoral Dissertations

Poly(acrylamidoxime) fibers are the current state-of-the-art adsorbent for mining uranium from seawater. However, the amidoxime group is not perfectly selective towards the uranyl cation, in particular, competition with transition metal cations remains a major challenge. In order for subsequent generations of chelating polymer adsorbents to be improved, the coordination chemistry of amidoxime-uranyl and -transition metal cation complexes needs to be better understood. While the coordination mode of amidoxime-uranyl complexes has been established in the literature, a number of amidoxime-transition metal cation complex binding motifs can be observed on the Cambridge Structrural Database. Likewise, the formation constants, or log K values, …

A Computational Study Of Small Gold Clusters With H2s, Thiols, H2o, And Alcohols, Silvija C. Smith

Theses and Dissertations (Comprehensive)

Alkane thiols, RSH, are commonly used in aqueous solution to stabilize and prevent aggregation of gold clusters, Au_n. Initially a RSH-Au_n complex is formed and, subsequently, there is hydrogen atom transfer to form a RSAu_nH complex. We examine the rate of this reaction for small neutral gold clusters, with n=1-2 and short-chain thiols with R = H, CH₃, and CH₃CH₂, using transition state theory. The comparison of DFT (with the functionals, BP86 and M06-2X), and MP2 was performed. A pseudopotential was employed to account for the large relativisitic effects …

Applying Computational Methods To Interpret Experimental Results In Tribology And Enantioselective Catalysis, Michael Garvey

Theses and Dissertations

Computational methods are rapidly becoming a mainstay in the field of chemistry. Advances in computational methods (both theory and implementation), increasing availability of computational resources and the advancement of parallel computing are some of the major forces driving this trend.

It is now possible to perform density functional theory (DFT) calculations with chemical accuracy for model systems that can be interrogated experimentally. This allows computational methods to supplement or complement experimental methods. There are even cases where DFT calculations can give insight into processes and interactions that cannot be interrogated directly by current experimental methods.

This work presents several examples …

Hindered Rotation Of Dihydrogen On Synthesized Metal Oxides, George Houston Rouvelas

Masters Theses

A MATLAB program was written to calculate the hindered rotational energies of the hydrogen and deuterium molecules interacting with an anisotropic potential, which may be thought of as a potential energy surface of a metal oxide substrate. It was found that an increase in the hindering potential of the rotation about the azimuthal angle lifted the degeneracy of the j = 1,mj [magnetic quantum number] = plus or minus 1 states. A better understanding of how the rotational states of these systems change as a function of the hindering potential can help to explain features in rotational inelastic neutron scattering …

Virtual Screening For Inhibitors Of Anti-Apoptotic Proteins: Dck, Bcl-Xl, Mcl-1, Mdmx, And Mdm2, Courtney Jerome Du Boulay

USF Tampa Graduate Theses and Dissertations

←Within this dissertation the topic of virtual screening is discussed with regard to three different cancer targets and also a brief introduction of the tools used in virtual screening. In Chapter 1, the reader will be introduced to virtual screening and the programs that are used in virtual screening. In Chapter 2, the first of three projects are discussed. This project consists of the work that was done to find inhibitors of the P53 binding domain of MDMX. In this project the mobility of residues within the binding site of MDMX are discussed and the ways in which we attempted …

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …

Development Of Improved Models For Gas Sorption Simulation, Keith Mclaughlin

USF Tampa Graduate Theses and Dissertations

Computational chemistry offers one the ability to develop a better understanding of the complex physical and chemical interactions that are fundamental to macro- and mesoscopic processes that are seen in laboratory experiments, industrial processes, and ordinary, everyday life. For many systems, the physics of interest occur at the molecular or atomistic levels, and in these cases, computational modeling and two well refined simulation techniques become invaluable: Monte Carlo (MC) and molecular dynamics (MD). In this work, two well established problems were tackled. First, models and potentials for various gas molecules were produced and refined from first principles. These models, although …

Solvation Energy Of Biomolecular Structures: A Study Of The Effect Of Salt On Biomolecules Through Implicit As Well As Explicit Solvation Methods, Mihir Date

All Dissertations

In the current dissertation, studies related to solvation energy of protein structures using implicit as well explicit solvation methods have been discussed. Special focus is given to explore effect of salt on the fold stability of proteins and enzymes. Salt plays a crucial role in the functioning of all proteins, enzymes and nucleic acids. Change in salt concentration of the medium has large impact on stability and activity of these biological macromolecules. Therefore exploring mechanism of salt effect on them and development of an efficient model to calculate the salt effect has fundamental as well as practical importance in the …