Physical Chemistry Commons^™

Computational Design Of Peptides And Proteins Through Machine Learning Approaches, Emily J. Hendrix

Chemistry and Chemical Biology ETDs

Advancements in machine learning have emerged as a pivotal tool in computational biochemistry, offering new advancements to address challenges in protein structure and function. However, current machine-learning approaches offer limited insight in understanding protein dynamics. The purpose of this work is to combine traditional physics-based computational tools, such as molecular dynamics and coarse-grained simulations, with recently developed AI-driven computational tools to bridge gaps and advance the understanding of proteins in both structural and dynamic aspects. I investigated several approaches such as (i) traditional physics-based methods to study protein conformation and ensembles; (ii) identifying a peptide inhibitor for the PICK1 PDZ …

Asphalt Pavement Rejuvenation Investigated By Nuclear Magnetic Resonance Relaxometry, Catherine Skaggs

Miners Solving for Tomorrow Research Conference

Asphalt is a relatively inexpensive material commonly used for road pavements; however, asphalt ages from exposure to oxygen and UV radiation, leading to loss of elasticity, which leads to cracks and potholes. To slow or reverse asphalt aging, pavement preservation treatments are in use. It’s unclear whether these treatments truly rejuvenate the pavement structure or merely offer a short-term benefit. Nuclear Magnetic Resonance (NMR) relaxometry is an analytical technique that uses the recovery of excited nuclear magnetization as a parameter to gain insights into molecular environments. Recovery-time distributions gathered from asphalt materials show differences between regular and rejuvenated asphalt samples, …

31p Solution Nmr Investigation Of Abasic Dna, Clarissa R. Krimmel

Graduate Theses/Dissertations

Base excision repair (BER) mechanisms fix single base lesions in DNA, such as T:G mismatches. During the base excision repair mechanism, an abasic site (AP site) is formed as an intermediate. AP sites are unstable and highly mutagenic; they can stop DNA replication. This research investigates how the conformational properties of abasic sites in DNA affect the binding recognition of enzymes involved in DNA repair mechanisms, including BER. Three different abasic sequences are being analyzed for this research project. A second project looks at the effects of a naturally occurring purine derivative, hypoxanthine, on the DNA backbone. These hypoxanthine lesions …

Interactions Of The Sars-Cov-2 Viral Genome 3’-Untranslated Region With Viral And Host Rnas, Caleb Frye, Mihaela Rita Mihailescu

Electronic Theses and Dissertations

This dissertation focuses on the characterization of RNA-RNA interactions within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome and with host microRNAs. As the causative agent of coronavirus disease 2019 (COVID-19), SARS-CoV-2 has evolved rapidly since its appearance. This has warranted prompt characterization of the virus particularly of its single stranded RNA (ssRNA) genome. By using a combination of bioinformatics, biophysics, and/or biological assays, we analyzed the SARS-CoV-2 viral genomic RNA and uncovered interactions of genomic RNA with host RNAs, highlighting an underutilized method of targeting RNA viruses. We showed here that the conserved elements in the viral genomic …

Incorporating Solvation Thermodynamic Mapping In Computer-Aided Drug Design, Yeonji Ji

Dissertations, Theses, and Capstone Projects

Advancements in computational techniques have revolutionized structure-based drug design, substantially improving the efficiency and effectiveness of the drug discovery process by reducing time, costs, and labor requirements. These advancements include various methods, such as investigating small molecule ligands binding to proteins, exploring alternative protein conformations, and solvation mapping on the protein surfaces. Among these methods, understanding the correlation between protein-ligand binding and the role of solvation is important.

A fundamental concept in protein-ligand binding is shape and electrostatic complementarity, which is complicated by the inherent flexibility of proteins. In the absence of small molecule ligands, proteins are complementary to surface …

Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave

Dissertations, Theses, and Capstone Projects

The challenge of establishing a sustainable and circular economy for materials in medicine and technology necessitates bioinspired design. Nature's intricate machinery, forged through evolution, relies on a finite set of biomolecular building blocks with through-bond and through-space interactions. Repurposing these molecular building blocks requires a seamless integration of computational modeling, design, and experimental validation. The tools and concepts developed in this thesis pioneer new directions in peptide-materials design, grounded in fundamental principles of physical chemistry. We present a synergistic approach that integrates experimental designs and computational methods, specifically molecular dynamics simulations, to gain in-depth molecular insights crucial for advancing the …

Binding Interactions Of Biologically Relevant Molecules Studied Using Surface-Modified And Nanostructured Surfaces, Palak Sondhi

Dissertations

This research focuses on the field of surface nanobioscience, wherein different nanosurfaces that will be used as working electrodes in the electrochemical cell are manufactured and surface modified to understand the critical binding interactions between biologically significant molecules like proteins, carbohydrates, small drug molecules, and glycoproteins. This research is essential if we are to determine whether a synthetic molecule can serve as a therapeutic candidate or diagnose a disease in its early stages. In order to fully understand the binding interactions, the study begins with defining some of the fundamental concepts, principles, and analytical tools for biosensing.

Afterwards, we addressed …

Substrate Specificity In Abc Transporters Using The E. Coli Methionine Import System, John H. Guardado

Featured Student Work

ATP-binding cassette (ABC) transporters use the energy of ATP to move substrates across membranes against a concentration gradient. The role of ABC transporters is crucial in several essential cellular functions and mutations in ABC transporters in humans have been linked to several conditions, including cystic fibrosis, liver disease, and diabetes. Despite their central roles in homeostasis, the mechanism of ABC transporters remains poorly understood. Our research is focused on studying an ABC importer in E. coli, as a model system, to examine the mechanism of substrate specificity and transport. The bacterial methionine import system consists of a membrane-embedded transporter, MetNI, …

Metals And Metal Complexes In Diseases With A Focus On Covid-19: Facts And Opinions, Agnieszka Ścibior, Manuel Aureliano, Alvin A. Holder, Juan Llopis

Chemistry & Biochemistry Faculty Publications

In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties. The Special Issue compiles data on the role of metals in COVID-19 and focuses on other illnesses and biological processes that affect metal metabolism. It consists of eight manuscripts, including five review articles and three original research papers (Figure …

Synthesis And Study Of High-Spin Stable Organic Radicals For Electrical Conductors And Mannosamine Nitroxide For Mri Contrast Agents, Shuyang Zhang

Department of Chemistry: Dissertations, Theses, and Student Research

In the first project, we describe the synthesis of an ambient stable high spin organic diradical 4 based on the Blatter moiety. The high-spin (S = 1) organic diradical 4, which consists of two Blatter radical moieties in a conjugated structure, exhibits a nearly exclusive population (88%) on triplet ground state at room temperature as a consequence of a large single-triplet energy gap (ΔEST = 0.5 kcal/mol). The target diradical molecule is synthesized over five steps with structural confirmation by single-crystal X-ray diffraction. The thermogravimetric analysis (TGA) shows the onset of decomposition at ~264 oC, indicating the diradical molecule has …

Structural Integrity And Stability Of Dna In Ionic Liquid And Near-Infrared Indolizine Squaraine Dye, Ember Yeji Suh

Honors Theses

Luminol, the most common presumptive test for blood at a crime scene, has multiple issues, such as false positive results with chemical agents, no luminescence due to “active oxygen” cleaning agents on bloodstains, and inability to penetrate textile materials. A combination of indolizine squaraine dye and ionic liquid (IL), or Dye Enhanced Textile Emission for Crime Tracking (DETECT), have shown potential to address these issues. The purpose of this study was to assess the binding mechanism of CG (1:1) and SO₃SQ dye to HSA and how the mechanism can explain the W214 fluorescence quenching effect and to determine …

A Synthetic Approach To The Optimization Of Silicon-Rosindolizine Swir Fluorophores, Timothy Lewis

Honors Theses

Fluorophores emitting within the near-infrared (700 – 1000 nm) or shortwave-infrared (1000 – 1700 nm) regions of the electromagnetic spectrum are of particular interest for their potential to supplement or even outright replace commonly used biological imaging techniques, such as magnetic resonance imaging and computed tomography scanning. Various characteristics make these molecules particularly appealing to researchers, such as their ease of synthetic tunability, generally low toxicity, and high solubility in biological media in comparison to other NIR- and SWIR-emissive fluorophores. Different molecular skeletons have been examined for use as the core of these imaging agents, such as squaraine, cyanine, and …

Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski

Graduate Theses/Dissertations

DNA damage, such as single base lesions and mismatches, is highly prevalent within cells. If these DNA damage events are not repaired, they could lead to mutations and thus disease and cancer. Intricate repair mechanisms are in place to fix these damage events, one such being Base Excision Repair (BER) and associated enzyme: Thymine DNA Glycosylase (TDG). The first step of this repair process, recognition of the lesion by TDG, is not well understood. The following thesis presents results to better understand the fundamental biophysical question of how a DNA lesion within a mismatch context is recognized in a million …

Food Waste Storage Gaseous Emissions Detection And Quantification Using Infrared Spectroscopy, Ryley A. Burton-Tauzer

Cal Poly Humboldt theses and projects

A growing interest in sustainable waste management and the implementation of new policies have prompted a shift towards alternative resource recovery methods for organic waste, including food waste. To effectively assess alternative food waste treatment scenarios, it is important to evaluate the life cycle impacts associated with each scenario. The storage phase of food waste, encompassing its accumulation in kitchens, and storage in bins for collection and transportation, has been overlooked as a source of greenhouse gases in previous studies. This investigation aimed to identify the greenhouse gases emitted during the initial five-day period of low-oxygen storage. An open dynamic …

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 …

Mechanism Of Sila- And Germafluorenes For Biological Applications, Shelby Jarrett

Dissertations

2,7-disubstituted silafluorenes and germafluorenes, originally designed for OLED applications, are a class of fluorescent dyes that have gained recent interest as probes for bioimaging and as biosensors to monitor cellular dynamics and interactions. Desirable biological probes absorb in the visible region, have high extinction coefficients, high quantum yield and excellent photostability. Here, their spectral properties are investigated under aqueous conditions for relevant biological applications. These molecules display intense blue fluorescence in the solid state and in solution, have high extinction coefficients, and exhibit appreciable solubility in aqueous solution. To better understand potential applications, the mechanism of fluorescence was investigated. It …

A New Insight Into Fungal Cell Wall Architecture By Functional Genomics And Solid-State Nmr Along With Recent Advancements In Dynamic Nuclear Polarization For Analyzing Biomolecules, Arnab Chakraborty

LSU Master's Theses

This dissertation summarizes the findings related to the way by which supramolecular architecture of fungal cell wall changes with genetic mutation, dispensing genes responsible for biosynthesis of cell wall polysaccharides. This is necessary because without perfect picture of how supramolecular assembly changes with genetic mutation it is hard to assess new anti-fungal targets. Alongside this we have highlighted how recent advancement into Dynamic Nuclear Polarization (DNP) methods improved characterization of biomolecules both in case of labeled and unlabeled samples.

First study utilized Solid-state NMR (SSNMR) which is a non-destructive technique hence enabled us for the first time to deduce how …

Analysis Of The Light Responsive Azobenzene Peptide Nucleic Acid Duplexes, Kat Nguyen

Honors College Theses

Peptide nucleic acids (PNAs) are oligonucleotide analogues in which the sugar-phosphate backbone has been replaced by a pseudopeptide skeleton. Since PNAs use the natural nucleobases (Adenine, Thymine, Cytosine, Uracil, and Guanine) found in either DNA and/or RNA, they are able to hybridize according to Watson-Crick base-pairing to form duplexes. PNA is a promising therapeutic agent because they can function as antigene or antisense chemical agents. To further enhance their utility, we aim to incorporate a photoswitchable moiety using azobenzene. Here, we report the results of the synthesis and purification of a photoswitchable 11 mer PNA along with initial characterization efforts.

Investigation Of The Binding Domain Interfaces Of The C-Terminus Of The Albino3 Insertase And The 43kda Chloroplast Signal Recognition Particle Subunit Via Single Molecule Förster Resonance Energy Transfer, Amanda Tomanek

Chemistry & Biochemistry Undergraduate Honors Theses

Fluorescent labeling is a technique used for visualizing functional groups contained in biomolecules by fluorescence imaging. This technique was used in this project to analyze post-translational targeting of light-harvesting chlorophyll-binding proteins (LHCP), which are the core complexes that harvest sunlight to drive photosynthetic electron transfer. This protein is synthesized in the cytosol and post-translationally targeted to the stroma of chloroplasts. CpSRP43 is a signal recognition particle (SRP) subunit unique to chloroplasts, which has been shown to interact with the stroma-soluble C-terminus of the thylakoid-bound Albino3 insertase (Alb3-Cterm). In the chloroplast stroma, targeting to thylakoids is performed via the cpSRP pathway …

Targeting Platelets Using Ionic Liquid Coated Nanoparticles, Karen Mun Wong

Honors Theses

Platelets are key players in our body’s inflammatory processes upon activation, which can create physiological problems. Researchers are actively seeking solutions by targeting platelets with therapeutics. The objective of the research in this thesis was to investigate a new and potentially less invasive drug delivery platform using nanoparticles. The topic of the project was to explore the world of ionic liquids and their abilities, when coated on nanoparticles, to bind to platelets. A library of choline carboxylic acid-based ionic liquids (ILs) was first synthesized via salt metathesis while PLGA-based nanoparticles were simultaneously being synthesized via the nanoprecipitation method. The ionic …

Affinity Of Cadmium Versus Zinc For The Carbonic Anhydrase Active Site, Rachel Phan

Honors Scholars Collaborative Projects

Cadmium is a heavy metal found in tobacco plants, nickel-cadmium batteries, and as a byproduct of metal mining. The similarities between the properties of zinc ions and cadmium ions in proteins due to their 2+ charges may cause displacement of zinc by cadmium if encountered and has been shown to do so in several transcription factors. Cadmium’s ability to replace zinc- a metal found in around 3,000 human proteins- is a cause for concern, especially due to its toxicity, long half-life in the body, and larger size.

Carbonic anhydrase is an important metalloprotein protein that relies on a central zinc(II) …

The Photo-Transformation Of Free Methionine In The Presence Of Surrogate And Standard Isolate Dissolved Organic Matter Under Sunlit Irradiation, Benjamin J. Mohrhardt

Dissertations, Master's Theses and Master's Reports

Sulfur (S)-containing amino acids are key sources of carbon, nitrogen, and sulfur involved in protein synthesis, protein function, and providing energy for microbial growth. Dissolved free and combined methionine is one of two S-containing amino acids incorporated into proteins and has been attributed to their stability and function. The oxidation of methionine has received considerable attention given its ubiquitous presence in most biological systems and has been associated with losses in protein function and pathological disorders. In natural waters, methionine is rapidly and selectively taken up by microorganisms to achieve cellular requirements of carbon, nitrogen, and sulfur. The abiotic transformation …

Investigations Of Elastin Recoil On Molecular And Macroscopic Levels., Nour Mohammad Jamhawi

Electronic Theses and Dissertations

Elastin is one of the most hydrophobic proteins, and it is extremely flexible when hydrated. The driving force for recoil is the decrease in entropy of the protein and/or the hydrating solvent. This dissertation is a study of both mechanisms. Following an introduction (Chapter 1), Chapters 2 and 3 investigate the recoil mechanism on the molecular level in the hydrating solvent and in the protein, respectively. Chapter 4 examines macroscopic properties of recoil by thermomechanics. Conclusions are discussed in Chapter 5. Using double quantum NMR, the deuterated water ordering at the elastin surface was studied quantitatively as a function of …

Bridging The 12-6-4 Model And The Fluctuating Charge Model, Pengfei Li

Chemistry: Faculty Publications and Other Works

Metal ions play important roles in various biological systems. Molecular dynamics (MD) using classical force field has become a popular research tool to study biological systems at the atomic level. However, meaningful MD simulations require reliable models and parameters. Previously we showed that the 12-6 Lennard-Jones nonbonded model for ions could not reproduce the experimental hydration free energy (HFE) and ion-oxygen distance (IOD) values simultaneously when ion has a charge of +2 or higher. We discussed that this deficiency arises from the overlook of the ion-induced dipole interaction in the 12-6 model, and this term is proportional to 1/r …

Mechanisms Of Spontaneous Curvature Inversion In Compressed Graphene Ripples For Energy Harvesting Applications Via Molecular Dynamics Simulations, James M. Mangum, Ferdinand Harerimana, Millicent N. Gikunda, Paul M. Thibado

Physics Faculty Publications and Presentations

Electrically conductive, highly flexible graphene membranes hold great promise for harvesting energy from ambient vibrations. For this study, we built numerous three-dimensional graphene ripples, with each featuring a different amount of compression, and performed molecular dynamics simulations at elevated temperatures. These ripples have a convex cosine shape, then spontaneously invert their curvature to concave. The average time between inversion events increases with compression. We use this to determine how the energy barrier height depends on strain. A typical convex-to-concave curvature inversion process begins when the ripple’s maximum shifts sideways from the normal central position toward the fixed outer edge. The …

High Performance Mixed-Matrix Electrospun Membranes For Ammonium Removal From Wastewaters, Shu-Ting Chen, Sumith Ranil Wickramasinghe, Xianghong Qian

Chemical Engineering Faculty Publications and Presentations

Mixed-matrix electrospun membranes were developed to investigate ammonium removal from low ammonium concentration wastewaters for the first time. Particles derived from the inexpensive zeolite 13X were successfully incorporated into polyethersulfone (PES) matrices. The fabricated mixed-matrix electrospun membranes demonstrate high ammonium removal capacity reaching over 55 mg/g_zeolite, more than 2.5 times higher than the previously fabricated mixed-matrix membranes via non-solvent induced phase inversion. Moreover, the membranes fabricated exhibit high permeability and ease of regeneration. Over 90% of total ammonium nitrogen (TAN) can be removed from low TAN wastewaters such as aquaculture wastewaters. In addition to zeolite 13X, other zeolite …

The Effect Of The Apolipoprotein A1 (Apoa1): The Stability And Folding In Potassium Chloride Environment, Alexandra Paladian

Honors Theses

Healthy levels of potassium chloride (KCl) can significantly affect the workings of the cholesterol level of the human body and how they pertain to an individual person. The search for a better salt additive for the human diet can provide a better option for people who experience high cholesterol levels and heart disease. The study focuses on the experimental design of the Molecular Dynamic (MD) simulation of the Apolipoprotein A1 (APOA1) in the potassium ion solution environment to determine the stability and folding of the protein. The study also compares its data to the previous experimental design of chloride ions …

Molecular Dynamic Simulation Of The Complex Folding Patterns Of Apolipoprotein A1 In Various Concentrations Of Potassium Chloride, Hannah Holmberg

Honors Theses

Apopliprotein or ApoA-1 is a complex lipoprotein that functions in the removal of cholesterol from the blood, removing cholesterol from the area around white blood cells and promoting the excretion of lipids through the lymphatic system. Previous research has found that ApoA-1 shows both folded and unfolded conformations depending on the concentration of NaCl in solution in the water around it. The protein was studied using molecular dynamics simulations. Once this state of equilibrium was reached, various structural properties of the protein were measured including the radius of gyration and the radial distribution function. The goal of the project was …

Remote Performance Modulation Of Ultrafiltration Membranes By Magnetically And Thermally Responsive Polymer Chains, Arijit Sengupta, Anh Vu, Xianghong Qian, Sumith R. Wickramasinghe

Chemical Engineering Faculty Publications and Presentations

Ultrafiltration membranes, that respond to an external magnetic field and local temperature have been developed. Surface-initiated activator-generated electron transfer (AGET) atom transfer radical polymerization (ATRP) has been used to graft poly(N-isopropylacrylamide) (PNIPAm) from the surface of 300 kDa regenerated cellulose membranes. The polymerization initiator was selectively attached to the entire membrane surface, only the outer membrane surface or only the inner pore surface. A superparamagnetic nanoparticle was attached to the end of the polymer chain. The DI water flux as well as the flux and rejection of bovine serum albumin were investigated in the absence and presence of a 20 …

Studies Of The Rectification Behavior Of The Pdt Ligand And The Active Site Of Msrp, Laura J. Ingersol

Chemistry and Chemical Biology ETDs

Molybdenum (Mo) is an essential element that plays an important role in global nitrogen, carbon, and sulfur cycles with a critical role in human metabolism and ecological balance. It becomes catalytically active when complexed with the pyranopterin dithiolene ligand (PDT), forming the nearly ubiquitous molybdenum cofactor (Moco). The complex biosynthetic pathway of Moco, its presence in all three domains of life, and its role as a constituent cofactor in the last universal common ancestor (LUCA) all point toward the importance of the PDT in the development of life on Earth. Molybdoenzymes catalyze the two-electron oxidation or reduction of substrates that …