Amino Acids, Peptides, and Proteins Commons^™

Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel

Dissertations, Theses, and Capstone Projects

Nucleosome core particles (NCP) are the building blocks that form a highly organized and compact chromatin structure. Nucleosomes package DNA in the nucleus of eukaryotic cells. The NCP consists of about 147 base pairs of DNA wrapped around the histone octamer, with 1.65 superhelical turns in a left-handed manner. The histone octamer is composed of two copies of H3, H4, H2A, and H2B. Together with histone H1 and linker DNA, they further assemble into a higher-order chromatin structure. The nucleosome complex is stabilized by electrostatic interactions between positively charged histone residues and the negatively charged DNA backbone. To effectively access …

Predicting And Decoding Allosteric Binding Sites Using Protein Language Models And Structure-Based Machine Learning: An Energy Landscape-Guided Explainable Ai Framework, Kamila Riedlová, Vít Skrhák, William G. Gatlin, Max Ludwick, Lucas Turano, Marian Novotný, David Hoksza, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Computational prediction of allosteric binding sites in protein structures remains a persistent challenge, as these regulatory pockets evade detection by both sequence-based and structure-based algorithms. Both computational and physical origins of this predictive asymmetry remain insufficiently understood. In this study, we systematically examine the determinants of binding site predictability using a dual framework that integrates a fine-tuned protein language model and the structure-based method P2Rank as complementary tools probing a diverse data set of 453 human kinases, together with a physics-based interpretability layer derived from energy landscape frustration analysis. Both predictors exhibit a sharp and reproducible dichotomy on protein kinases, …

Herbularyo (Folk Healer): An Herbal Medicine Card Game, Maryjane T. Magsino, Inah Marie Q. Rivera, Armando M. Guidote, Genejane M. Adarlo

Chemistry Faculty Publications

Herbularyo, a card game teaching about herbal plants (HPs), was created and evaluated as a viable educational card game based on Tuomisto and Aksela’s criteria. A quasi-experiment was performed on 81 Grade 8 students from a private high school and 50 Grade 11 from a public high school. Independent t-test revealed that the control group (CG) and experimental group (EG) (p=0.386), and EG1 (played ≤5) and EG2 (played >5) (p=0.681) are not comparable with each other. Paired t-test showed EG performed better (p=0.001) than CG (p=0.901) whereas ANCOVA showed that playing Herbularyo improved students’ information retention (p=0.006). EG1 and EG2 …

Increased Backbone Rigidity Of Artificial Transcription Factors, Jasmine Glover, Emma Otey, Joanna K. Kwao, Nicholas Truex

Senior Theses

Programming DNA-binding proteins is an effective strategy for developing therapeutics that regulate gene expression. These proteins can directly bind to DNA to activate or repress transcription of specific genes. Zinc finger proteins are a class of DNA-binding proteins commonly found in eukaryotic organisms. Their DNA-binding function is derived from unique amino acid sequences within each domain that recognizes specific nucleotides, allowing each finger to selectively recognize three DNA base pairs. Adjoining of multiple domains in tandem allows recognition of a specific DNA sequence. Artificial transcription factors can be made of multiple zinc finger domains arranged in tandem and engineered to …

From Latent Manifolds To Targeted Molecular Probes: An Interpretable, Kinome-Scale Generative Machine Learning Framework For Family-Based Kinase Ligand Design, Gennady M. Verkhivker, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

Scaffold-aware artificial intelligence (AI) models enable systematic exploration of chemical space conditioned on protein-interacting ligands, yet the representational principles governing their behavior remain poorly understood. The computational representation of structurally complex kinase small molecules remains a formidable challenge due to the high conservation of ATP active site architecture across the kinome and the topological complexity of structural scaffolds in current generative AI frameworks. In this study, we present a diagnostic, modular and chemistry-first generative framework for design of targeted SRC kinase ligands by integrating ChemVAE-based latent space modeling, a chemically interpretable structural similarity metric (Kinase Likelihood Score), Bayesian optimization, and …

Allosteric Control Overcomes Steric Limitations For Neutralizing Antibodies Targeting Conserved Binding Epitopes Of The Sars-Cov-2 Spike Protein: Exploring The Intersection Of Binding, Allostery, And Immune Escape With A Multimodal Computational Approach, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Understanding the atomistic basis of multi-layer mechanisms employed by broadly reactive neutralizing antibodies of the SARS-CoV-2 spike protein without directly blocking receptor engagement remains an important challenge in coronavirus immunology. Class 4 antibodies represent an intriguing case: they target a deeply conserved, cryptic epitope on the receptor-binding domain yet exhibit variable neutralization potency across subgroups F1 (CR3022, EY6A, COVA1-16), F2 (DH1047), and F3 (S2X259). The molecular basis for this variability is not fully understood. Here, we employed a multi-modal computational approach integrating atomistic and coarse-grained molecular dynamics simulations, binding free energy calculations, mutational scanning, and dynamic network analysis to elucidate …

Dynamic Mutational Profiling Of Binding Interactions And Allosteric Networks In Conformational Ensembles Of The Sars-Cov-2 Spike Protein Complexes With Classes Of Antibodies Targeting Cryptic Binding Sites: Confluence Of Binding And Allostery Determines Molecular Mechanisms And Hotspots Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could underlie complexity of broad and escape-resistant neutralization. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how Class 4 antibodies (represented by S2X35, 25F9, and SA55) and Class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the …

A Mutational Analysis Of Thatisin: How Single Point Mutations Impact The Biosynthetic Process Of A Group 16 Graspetide, John F. Boynton Jr

Chemistry and Chemical Biology ETDs

Abstract:

Graspetides are a family of Ribosomally synthesized and Post-translationally modified Peptide (RiPP) natural products named for their ATP Grasp Macrocyclases. We identified several Graspetide Biosynthetic Gene Clusters containing common double glycine cleavage motifs and attempted characterization of the mature Graspetides. One of the resulting peptides, Thatisin, has a topology with two interlocking macrolactones installed by a single ATP Grasp Ligase named ThtC. Here we use single and double point mutations to observe the impact or variation on the installation of these macrocycles. Alanine scan mutagenesis is used to assess leader peptide residues in the precursor peptide ThtA to determine …

Ensemble-Based Binding Free Energy Profiling And Network Analysis Of The Kras Interactions With Darpin Proteins Targeting Distinct Binding Sites: Revealing Molecular Determinants And Universal Architecture Of Regulatory Hotspots And Allosteric Binding, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

KRAS is a pivotal oncoprotein that regulates cell proliferation and survival through interactions with downstream effectors such as RAF1. Despite significant advances in understanding KRAS biology, the structural and dynamic mechanisms of KRAS allostery remain poorly understood. In this study, we employ microsecond molecular dynamics simulations, mutational scanning, and binding free energy calculations together with dynamic network modeling to dissect how engineered DARPin proteins K27, K55, K13, and K19 engage KRAS through diverse molecular mechanisms ranging from effector mimicry to conformational restriction and allosteric modulation. Mutational scanning across all four DARPin systems identifies a core set of evolutionarily constrained residues …

Integrative Computational Modeling Of Distinct Binding Mechanisms For Broadly Neutralizing Antibodies Targeting Sars-Cov-2 Spike Omicron Variants: Balance Of Evolutionary And Dynamic Adaptability In Shaping Molecular Determinants Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we conducted a comprehensive analysis of the interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and four neutralizing antibodies—S309, S304, CYFN1006, and VIR-7229. Using integrative computational modeling that combined all-atom molecular dynamics (MD) simulations, mutational scanning, and MM-GBSA binding free energy calculations, we elucidated the structural, energetic, and dynamic determinants of antibody binding. Our findings reveal distinct dynamic binding mechanisms and evolutionary adaptation driving the broad neutralization effect of these antibodies. We show that S309 targets conserved residues near the ACE2 interface, leveraging synergistic van der Waals and electrostatic interactions, while S304 focuses on …

Probing Binding And Allosteric Mechanisms Of The Kras Interactions With Monobodies And Affimer Proteins : Ensemble-Based Mutational Profiling And Thermodynamic Analysis Of Binding Energetics And Allostery Reveal Diversity Of Functional Hotspots And Cryptic Pockets Linked By Conserved Communication Network, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Guang Hu, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

KRAS, a historically "undruggable" oncogenic driver, has eluded targeted therapies due to its lack of accessible binding pockets in its active state. This study investigates the conformational dynamics, binding mechanisms, and allosteric communication networks of KRAS in complexes with monobodies (12D1, 12D5) and affimer proteins (K6, K3, K69) to characterize the binding and allosteric mechanisms and hotspots of KRAS binding. Through molecular dynamics simulations, mutational scanning, binding free energy analysis and network-based analyses, we identified conserved allosteric hotspots that serve as critical nodes for long-range communication in KRAS. Key residues in β-strand 4 (F78, L80, F82), α-helix 3 (I93, H95, …

Quantitative Characterization And Prediction Of The Binding Determinants And Immune Escape Hotspots For Groups Of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling Of The Sars-Cov-2 Spike Complexes With Antibodies, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by the balance and tradeoff between multiple energetic factors and interaction contributions of the evolving escape hotspots involved in antigenic drift and convergent evolution. However, the dynamic and energetic details quantifying the balance and contribution of these factors, particularly the balancing nature of specific interactions formed by antibodies with epitope residues, remain largely uncharacterized. In this study, we performed molecular dynamics simulations, an ensemble-based deep mutational scanning of SARS-CoV-2 spike residues, and binding free energy computations for two distinct groups …

Asymmetric Synthesis Of The Hiv Protease Inhibitor Tmc-126 And An Anti-Malarial Agent Via A Titanium Tetrachloride Mediated Asymmetric Glycolate Aldol Addition Reaction. Redefining The Curtius Rearrangement Reaction Via Dehomologation Of Carboxylic Acids Bearing Alpha-Leaving Groups, Kweku Amaning Affram

Theses and Dissertations

Acquired Immune Deficiency Syndrome (AIDS) and malaria are two devastating infectious diseases caused by HIV and Plasmodium parasites. AIDS is caused by HIV-1 and HIV-2, transmitted through sexual contact, blood transfusions, needle sharing, and perinatal routes. Malaria, caused by plasmodium parasites through mosquito bites. Today, millions of people around the world have been infected with HIV and malaria and much research has been done to treat it. However, despite advancements in therapeutic options, these diseases remain a significant global health threat, particularly in developing countries due to the emergence of drug-resistant strains for both HIV and malaria complicating eradication efforts. …

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

Deciphering The Chemistry Of Condensed Aromatic "Black" Carbon And Nitrogen In Amazonian Anthrosols, João Vitor Dos Santos, Aleksandar I. Goranov, Laís G. Fregolente, Marcia C. Bisinoti, Zhenhuan Sun, Klaus Schmidt-Rohr, Patrick G. Hatcher

Chemistry & Biochemistry Faculty Publications

Amazonian anthrosols are renowned for their high fertility and dark color, properties primarily attributed to the abundance of condensed aromatic carbon (ConAC) in the soil organic matter. ConAC, commonly referred to as black carbon, play a key role in the stability and nutrient retention of these soils. However, the processes governing the formation of ConAC and its transformation into oxygenated derivatives remain poorly understood. In this study, we used multiple analytical platforms to investigate the chemistry of ConAC-rich humic acids (HA) extracted from Terra Mulata de Indio, a type of Amazonian anthrosol. The results reveal that ConAC are predominantly …

Interaction Of Cardiac Leiomodin With The Native Cardiac Thin Filament, Madison Little, Cristina M. Risi, Tania M. Larrinaga, Mason D. Summers, Tyler Nguyen, Garry E. Smith Jr., Jennifer Atherton, Carol C. Gregorio, Alla S. Kostyukova, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Every heartbeat depends on cyclical contraction-relaxation produced by the interactions between myosin-containing thick and actin-based thin filaments (TFs) arranged into a crystalline-like lattice in the cardiac sarcomere. Therefore, the maintenance of thin filament length is crucial for myocardium function. The thin filament is comprised of an actin backbone, the regulatory troponin complex and tropomyosin that controls interactions between thick and thin filaments. Thin filament length is controlled by the tropomodulin family of proteins; tropomodulin caps pointed ends of thin filaments, and leiomodin (Lmod) promotes elongation of thin filaments by a “leaky-cap” mechanism. The broader distribution of Lmod on the thin …

Structural Optimization And Stability Enhancement Of Uba(2) And Ntl9 Using The Computational Tool: Emcast, Bahar Ghazi Esfahani

Graduate Student Theses, Dissertations, & Professional Papers

This study enhances protein stability prediction by refining EmCAST (Empirical C-Alpha Stability Tool), a computational tool used to identify stabilizing mutations in protein domains. We applied EmCAST to two model proteins: the α-helical ubiquitin-associated domain 2 (UBA(2)) and the α/β N-terminal domain of ribosomal protein L9 (NTL9). Protein stability is critical for proper function, and mutations can lead to misfolding and disease. To validate EmCAST’s predictions, guanidine hydrochloride-induced denaturation was monitored using circular dichroism (CD) spectroscopy for both wild-type and mutant variants. Results guided refinements to EmCAST’s algorithm, incorporating new experimental datasets to improve accuracy. Additionally, we examined the assumption …

Redox Control In A Fused Electron Transfer Flavoprotein From A Thermophilic Archaeon And Expanded Significance Of A Hydrogen Bond From A Conserved Histidine Residue That Contributes To Flavin Redox Tuning And Activation For Covalent Modification, Debarati Das

Theses and Dissertations--Chemistry

In absence of O₂ as terminal electron acceptors in anaerobic bacteria and archaea, carbohydrate metabolism is 15 times less efficient compared to aerobic energy metabolism resulting in energy deficit conditions. Despite their meager resources these anaerobes were able to generate H₂ and a chemiosmotic potential able to drive energy demanding reactions such as CO₂ or N₂ fixation. These observations raised concerns as production of high energy reductants (H₂) from mediocre fuels (NADH) defied the laws of thermodynamics.

In 2008, a known mechanism “electron bifurcation” but with flavins as redox mediators instead of quinones was …

Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)₄-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn²⁺ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the …

Assembly Of Ppsu-Oligomers, Mariam Nesterov

Student Theses and Dissertations

The development of nanostructures for delivering multiple proteins to targeted antibodies has become a promising avenue in biotechnology, driven by advancements in synthetic polymers like poly(propylene sulfone), PPSU. However, the PPSU polymer faces a major limitation - its high insolubility. To address this challenge, this study investigates whether PPSU oligomers can enhance both the solubility and stability of lysozyme, a model protein that is cost-effective and widely accessible. Using dimer, trimer, tetramer, and hexamer configurations, we analyzed the interactions between PPSU oligomer and lysozyme under varying conditions. Our results show that the dimer and trimer are water soluble (no aggregate …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Alphafold2-Based Characterization Of Apo And Holo Protein Structures And Conformational Ensembles Using Randomized Alanine Sequence Scanning Adaptation: Capturing Shared Signature Dynamics And Ligand-Induced Conformational Changes, Nishank Raisinghani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Proteins often exist in multiple conformational states, influenced by the binding of ligands or substrates. The study of these states, particularly the apo (unbound) and holo (ligand-bound) forms, is crucial for understanding protein function, dynamics, and interactions. In the current study, we use AlphaFold2, which combines randomized alanine sequence masking with shallow multiple sequence alignment subsampling to expand the conformational diversity of the predicted structural ensembles and capture conformational changes between apo and holo protein forms. Using several well-established datasets of structurally diverse apo-holo protein pairs, the proposed approach enables robust predictions of apo and holo structures and conformational ensembles, …

Alphafold2 Modeling And Molecular Dynamics Simulations Of The Conformational Ensembles For The Sars-Cov-2 Spike Omicron Jn.1, Kp.2 And Kp.3 Variants: Mutational Profiling Of Binding Energetics Reveals Epistatic Drivers Of The Ace2 Affinity And Escape Hotspots Of Antibody Resistance, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

AlphaFold2-based atomistic predictions of structures and conformational ensembles of the SARS-CoV-2 spike complexes with the host receptor ACE2 for the most dominant Omicron variants JN.1, KP.1, KP.2 and KP.3 to examine the mechanisms underlying the role of convergent evolution hotspots in balancing ACE2 binding and antibody evasion. Using the ensemble-based mutational scanning of the spike protein residues and computations of binding affinities, we identified binding energy hotspots and characterized the molecular basis underlying epistatic couplings between convergent mutational hotspots. The results suggested the existence of epistatic interactions between convergent mutational sites at L455, F456, Q493 positions that protect and restore …

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 …

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

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 …

The Kinetic Modulation Of Α - Synuclein Fibrillation And Toxicity By 4-Phenylbutyric Acid, Kristos Awuah Baffour

Graduate Theses/Dissertations

ABSTRACT

The Protein misfolding and aggregation of alpha-synuclein (α-syn) into neurotoxic amyloids underlies the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). 4-Phenylbutyrate (PBA), an FDA drug approved for treating urea cycle disorders, has garnered significant attention as a potential chemical chaperone for targeting alpha-synuclein (α-syn) aggregation. Using in vitro assays, we demonstrated that PBA treatment alters the pattern of α-syn aggregation, as evidenced by reduced formation of oligomeric species and its increased susceptibility to proteolytic cleavage under the influence of PBA. Proteinase K assay, surface plasmon resonance, and Nile red studies indicate that PBA interacts with the extensive …

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

Hybridization Kinetics Of Four-Way Junctions Localized On A Dna Scaffold, Katherine N. Taylor

Honors Undergraduate Theses

DNA computing is an ever-growing field with scientists trying to design structures that optimize logic gate communication to develop fast, biologically compatible, computational structures. We hypothesize that by using the principles of DNA computing, it is possible to design a DNA tile capable of studying localized DNA hybridization that can differentiate between oligonucleotides of different structural conformations. This includes synthetically manipulating DNA into a nanostructure that can perform Boolean logic functions to calculate the different rates of hybridization. To test our hypothesis, we designed a DNA Tile that incorporated a 4WJ using YES logic. Linear and hairpin single-stranded (ss) DNA …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …