Other Chemistry Commons^™

Β-Sheets Mediate The Conformational Change And Allosteric Signal Transmission Between The Aslov2 Termini, Sian Xiao, Mayar Terek Ibrahim, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

Avena sativa phototropin 1 light-oxygen-voltage 2 domain (AsLOV2) is a model protein of Per-Arnt-Sim (PAS) superfamily, characterized by conformational changes in response to external environmental stimuli. This conformational change begins with the unfolding of the N-terminal A'α helix in the dark state followed by the unfolding of the C-terminal Jα helix. The light state is characterized by the unfolded termini and the subsequent modifications in hydrogen bond patterns. In this photoreceptor, β-sheets are identified as crucial components for mediating allosteric signal transmission between the two termini. Through combined experimental and computational investigations, the Hβ …

De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, Dony Ang, Cyril Rakovski, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards …

Variables Affecting The Extraction Of Antioxidants In Cold And Hot Brew Coffee: A Review, Brian Yust, Frank Wilkinson, Niny Rao

College of Life Sciences Faculty Papers

Coffee beans are a readily available, abundant source of antioxidants used worldwide. With the increasing interest in and consumption of coffee beverages globally, research into the production, preparation, and chemical profile of coffee has also increased in recent years. A wide range of variables such as roasting temperature, coffee grind size, brewing temperature, and brewing duration can have a significant impact on the extractable antioxidant content of coffee products. While there is no single standard method for measuring all of the antioxidants found in coffee, multiple methods which introduce the coffee product to a target molecule or reagent can be …

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Development Of A Methodology For The Quantification Of Reaerosolization Of A Biological Contaminate Surrogate Particle From A Military Uniform Fabric, George Cooksey, Jeremy M. Slagley, Casey W. Cooper, Douglas Lewis, Alisha Helm

Faculty Publications

In a mass casualty medical evacuation after a bioaerosol (BA) dispersal event, a decontamination (DC) method is needed that can both decontaminate and prevent biological particle (BP) re-aerosolization (RA) of contaminated clothes. However, neither the efficacy of current DC methods nor the risk of BP RA is greatly explored in the existing literature. The goals of this study were to develop a repeatable method to quantify the RA of a biological contaminant off military uniform fabric swatches and to test the efficacy of one DC protocol (high-volume, low-pressure water) using 1 µm polystyrene latex (PSL) spheres as a surrogate. A …

Photodynamic Therapy Agents: The Power Of Mjöllnir To Eradicate Cancer, Sidney M. Hopper

Honors College Theses

After its discovery back in the 1900s, photosensitizers became a critical study for potential treatments and cures for medical issues, including cancer. It was discovered that porphyrins appeared to target and accumulate in proliferating cells, and to reach the cells, a certain wavelength of light with maximum absorbance associated with the porphyrin was necessary to achieve cell death. Photodynamic therapy involves making use of porphyrins or metalloporphyrins as activators when exposed to such light. When activated, these compounds generate reactive oxygen species (ROS), such as HO- or O2-, which can react with nucleic acids found in DNA and RNA. In …

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …

Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

Peptidomics Analysis Reveals Changes In Small Urinary Peptides In Patients With Interstitial Cystitis/Bladder Pain Syndrome, Md Shadman Ridwan Abid, Haowen Qiu, Bridget Tripp, Aline De Lima Leite, Heidi E. Roth, Jiri Adamec, Robert Powers, James W. Checco

Chemistry Department: Faculty Publications

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating pain disorder of the bladder and urinary tract with poorly understood etiology. A definitive diagnosis of IC/BPS can be challenging because many symptoms are shared with other urological disorders. An analysis of urine presents an attractive and non-invasive resource for monitoring and diagnosing IC/BPS. The antiproliferative factor (APF) peptide has been previously identified in the urine of IC/BPS patients and is a proposed biomarker for the disorder. Nevertheless, other small urinary peptides have remained uninvestigated in IC/BPS primarily because protein biomarker discovery efforts employ protocols that remove small endogenous peptides. …

Aptamer-Based Voltammetric Biosensing For The Detection Of Codeine And Fentanyl In Sweat And Saliva, Rosa Lashantez Cromartie

FIU Electronic Theses and Dissertations

Despite the many governmental and medicinal restrictions created to combat the opioid epidemic in the United States, opioid abuse and overdose rates continue to rise. The development of an aptamer-based voltammetric sensor and biosensor is described in this dissertation. The aim was to develop a low-cost, sensitive, and specific aptamer-based sensor for on-site, label-free determination of codeine and fentanyl in biological fluids. To do this, the surfaces of screen-printed carbon electrodes (SPCE) were modified with gold nanoparticles (AuNPs), followed by the addition of single-stranded DNA aptamers. These were covalently bound to the electrode surface. Operations of the sensors were collected …

Cyclic Peptide-Gadolinium Nanocomplexes As Sirna Delivery Tools, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Dindyal Mandal, David Stickley, Stephanie Nagasawa, Joshua Long, Sandeep Lohan, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)₅C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)₅C]-GdNPs, in the range of 240 to 260 nm upon mixing with an aqueous solution of GdCl₃. Herein, we report [(WR)₅C]-GdNPs as an efficient siRNA delivery system. The peptide-based gadolinium nanoparticles (50 µM) did not exhibit significant cytotoxicity (~93% cell viability at 50 µM) in human leukemia T lymphoblast cells (CCRF-CEM) and triple-negative breast cancer cells (MDA-MB-231) after 48 h. Fluorescence-activated cell sorting (FACS) analysis indicated …

Atomistic Simulations And In Silico Mutational Profiling Of Protein Stability And Binding In The Sars-Cov-2 Spike Protein Complexes With Nanobodies: Molecular Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structure-functional studies have recently revealed a spectrum of diverse high-affinity nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we combine atomistic simulations with the ensemble-based mutational profiling of binding for the SARS-CoV-2 S-RBD complexes with a wide range of nanobodies to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations. Using an in silico mutational profiling approach for probing the protein stability and binding, we examine dynamics and energetics of the SARS-CoV-2 complexes with single nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E + …

Enhanced Platinum (Ii) Drug Delivery For Anti-Cancer Therapy, Marek T. Wlodarczyk

Dissertations, Theses, and Capstone Projects

Over the years, anti-cancer therapies have improved the overall survival rate of patients. Nevertheless, the traditional free drug therapies still suffer from side effects and systemic toxicity, resulting in low drug dosages in the clinic. This often leads to suboptimal drug concentrations reaching cancer cells, contributing to treatment failure and drug resistance. Among available anti-cancer therapies, metallodrugs are of great interest. Platinum (II)-based agents are highly potent and are used to treat many cancers, including ovarian cancer (OC). Cisplatin (cis-diaminedichloroplatinum (II)) is the first Food and Drug Administration (FDA)-approved metallodrug for treatment of solid tumors, and its mechanism …

Correlation Effects On Intramolecular C-H...Oh And O-H...O Hydrogen Bond Interactions In Azelaic Acid: An Ab Initio Study, Sabina Kalata, Alina Huang, Ruben Parra

DePaul Discoveries

Electron correlation effects on both conventional, O-H…O, and nonconventional, C-H…O, intramolecular hydrogen bonds present in a selected azelaic acid folded conformation were evaluated ab initio using HF and MP2 methodologies. The relative strength of the hydrogen bonds was examined through different indicators derived from geometry, vibrational frequencies, and electron density along the hydrogen bond path. The HF method results in weaker O-H…O and C-H…O hydrogen bonds when compared with the corresponding results using the MP2 method. Additionally, the stability of the folded azelaic conformation is found to depend on the level of theory used. Accordingly, the zero-point corrected energies of …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Transcriptional Repressor Protein Based Macrolide Biosensor Development With Improved Sensitivity, Jayani A. Christopher

Graduate Research Posters

Macrolide antibiotics are in high demand for clinical applications. Macrolides are biosynthesized via giant assembly line polyketide synthases (PKS) which are arranged in a modular fashion. Combinatorial biosynthetic methods have been used to produce diversified macrolides by reprograming these modules and modifying tailoring enzymes required for post synthetic modifications. However it is challenging due to the size and complexity of PKSs. To overcome this challenge, new enzymes for macrolide diversification could be obtained by directed evolution where a large number of enzyme variants need to be screened. Therefore it is important to develop high throughput screening methods to identify the …

Carbon Dioxide And Particulate Matter Concentration On Hampton Roads Air Quality, Gregory Hubbard

OUR Journal: ODU Undergraduate Research Journal

Hampton Roads has been a maritime crossroads for the last 400 years. Industrialization has impacted the coastal region for the last 250 years. The expansion of the Port of Virginia in 2019 has created dense traffic in the region resulting in impacts to air quality. Two waste products that affect humans are particulate matter and carbon dioxide. Both respective emissions can cause adverse effects on humans, such as asthma, some lung cancers, and other respiratory distress. Scientists and health practitioners are studying the effects of particulate matter on human health. Hampton Roads, in particular, because of its unique location on …

Development Of Computational Tools To Target Microrna, Luo Song

Dissertations & Theses (Open Access)

MicroRNAs (a.k.a, miRNAs) play an important role in disease development. However, few of their structures have been determined and structure-based computational methods remain challenging in accurately predicting their interactions with small molecules. To address this issue, my thesis is to develop integrated approaches to screening for novel inhibitors by targeting specific structure motifs in miRNAs. The project starts with implementing a tool to find potential miRNA targets with desired motifs. I combined both sequence information of miRNAs and known RNA structure data from Protein Data Bank (PDB) to predict the miRNA structure and identify the motif to target, then I …

Coevolution, Dynamics And Allostery Conspire In Shaping Cooperative Binding And Signal Transmission Of The Sars-Cov-2 Spike Protein With Human Angiotensin-Converting Enzyme 2, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Binding to the host receptor is a critical initial step for the coronavirus SARS-CoV-2 spike protein to enter into target cells and trigger virus transmission. A detailed dynamic and energetic view of the binding mechanisms underlying virus entry is not fully understood and the consensus around the molecular origins behind binding preferences of SARS-CoV-2 for binding with the angiotensin-converting enzyme 2 (ACE2) host receptor is yet to be established. In this work, we performed a comprehensive computational investigation in which sequence analysis and modeling of coevolutionary networks are combined with atomistic molecular simulations and comparative binding free energy analysis of …

Design And Synthesis Of Core–Shell Microgels With One‐Step Clickable Crosslinked Cores And Ultralow Crosslinked Shells, Molla R. Islam, Chelsea Nguy, Sanika Pandit, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The present study is conducted to explore the engineering of core–shell microgels such that the core can be rapidly labeled with a variety of fluorophores, while the shell retains the softness needed in specific biomedical applications. Azide containing crosslinked core particles based on a crosslinked poly(N‐isopropylacrylamide) particle, using a one‐pot, multistep polymerization is synthesized. A core–shell microgel is then synthesized by growing a crosslinker‐free poly(N‐isopropylacrylamide)‐co‐acrylic acid (ULC10AAc) shell through a two‐step seed and feed polymerization. A simple “click” reaction between the azide present on the core and dibenzocyclooctyne containing fluorophores to make dyed core–shell …

Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT₃) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC₅₀ = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT₃ antagonist [³H]GR65630, indicating that it is a noncompetitive inhibitor of …

Mapping Gadolinium Contrast In A Complex Ionic And Photosynthesis Environment Of Pineapple By Near-Infrared And X-Ray Imaging, Subhendra Sarkar, Zoya Vinokur, Chen Xu, Tetiana Soloviova, Amina Shahbaz, Aldona Gjoni

Publications and Research

This work explores the diffusivity of a lanthanide complex, Eovist (Gadolinium-Ethoxy Benzyl Diethylenetriamine pentaacetate) that is stable in neutral media but is not in acidic environment. In the current work an acidic fruit model like pineapple that is rich in transition metals was used and a possible transmetallation reaction among Eovist and transition metal complexes was tested using X-ray imaging. Another goal of this work was to perturb the usual and the unusual photosynthesis systems that pineapple has maintained for millions of years during the evolution of circadian genes for efficient water conservation by dark photosynthesis. To detect such photosynthesis …

I. Non-Degradable Polysiloxane Networks For Controlled Release Applications, And Ii. Additive Free, Degradable Silyl-Ether Furyl-Maleimide Networks, Caleb M. Bunton

Chemistry Theses and Dissertations

I. Two different series of non–degradable polysiloxane networks were prepared for the encapsulation and controlled release of a small molecule agent. For the first series, hydrosilylation was utilized to prepare networks of varying crosslink densities, as determined from swelling studies, from vinyl terminated and silylhydride functional poly(dimethyl)siloxanes. For the second series, the thiol-ene reaction was utilized to prepare networks of varying crosslink densities, as determined from swelling studies, from vinyl terminated and mercaptopropyl functional poly(dimethyl)siloxanes. Nile red dye was used as an encapsulated agent and dye release from each series of networks was measured using UV–vis spectroscopy to determine controllability …

Biological Evaluation Of Fda-Approved Drugs As Mirna-31 Inhibitors Using Real Time Qrt-Pcr And A Luciferase Assay, Nicholas Sienkiewicz

Honors Theses

MicroRNAs (miRNAs) are a group of post-transcriptional, negative regulators of gene expression, consisting of ~19-24 nucleotides. Since their discovery in 1993, miRNAs have been found to be involved in a diverse amount of cellular and disease pathways, including certain types of cancer. Overexpression of certain oncogenic miRNAs, including miRNA-31, have been shown to play a role in cancer cell development. Recent findings have suggested that miRNAs play a significant role in every stage of colorectal cancer (CRC) initiation, progression, and development, as well as induce resistance to chemotherapy drugs like 5-FU. In particular, research has shown that increased levels of …

Characterization Of Dimerization Domains On The Mannose-6-Phosphate/Insulin-Like Growth Factor 2 Receptor, Tyler Degener

UNO Student Research and Creative Activity Fair

The mannose-6-phosphate/insulin-like growth factor 2 (M6P/IGF2) receptor is a transmembrane protein with the ability to sequester growth factors from the extracellular matrix. This behavior links the receptor to tumor suppression. On a structural level, the extracellular portion of the protein is segmented into 15 homologous repeats, which can be divided further into 5 triplet domains, labelled 1-3, 4-6, 7-9, 10-12, and 13-15. Each triplet receptor displays its own unique ligand binding affinity, including the ability to form dimers with triplets on a second M6P/IGF2 receptor. In fact, previous studies indicate that this protein functions optimally when dimerized. Thus, the purpose …

Using Batman Software To Analyze Metabolic Changes In Type 1 Diabetes-Susceptible Rats, Connor Hall

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Kidney Tissue Preparation For 1h-Nmr Analysis And Colorimetric Activity Assay Of Mitochondria, Savannah Knight, James Wolfsberger

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Lew,1wr1 Rat Shows An Increased Risk Of Developing Malignant Forms Of Nafld, Luis Mercado

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …