Biochemistry, Biophysics, and Structural Biology Commons^™

Sec-Saxs And Sans Analyses Of The Talin•Vinculin Complex, Gilbert Reyes

Dissertations, Theses, and Capstone Projects

Focal adhesions (FA) are integrin-based cell-matrix adhesion sites composed of adaptor proteins that facilitate the generation of traction forces important for biological functions such as cell migration, embryo development, wound healing, tissue organization and stability, and immune responses. Mature FA are observed when both autoinhibited multi-domain scaffolding protein talin and membrane-cytoskeletal protein vinculin are activated and interact thus promoting the assembly and function of FA. While research has resolved truncated sections of autoinhibited talin and recruitment of vinculin due to mechanotransduction that exposes cryptic vinculin binding sites (VBS), little is known about the global modifications of full length talin in …

Identifying Textual Predictors Of Early Termination In Clinical Trials In Medicine: An Explainable Machine-Learning Study, Rohan Ramnarain

Dissertations, Theses, and Capstone Projects

About one in five clinical trials in medicine ends early, wasting valuable resources and reducing the evidence available for developing life-saving medical treatments. This project uses a method called Trial2Vec, which is a self-supervised machine-learning method that converts clinical trial documents into dense numerical representations that capture their key design and clinical characteristics, to turn each proposed clinical trial’s written protocol into a compact numerical profile (a process referred to as embedding). These profiles are then paired with a predictive machine learning models to identify the words and phrases in the trial documents that can signal a higher risk of …

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 …

Supramolecular Assembly In Short Peptide Systems For Selective Metabolite Recognition And Drug Nanoencapsulation, Maithreyi Ramakrishnan

Dissertations, Theses, and Capstone Projects

Short peptides can form adaptive supramolecular assemblies, and understanding how minimal sequences organize around neurometabolites or hydrophobic cancer drugs enables the rational design of functional materials. This thesis combines molecular dynamics with experimental validation to establish design rules linking peptide sequence to emergent structure and function. Chapter 1 outlines the molecular determinants governing peptide assembly. Chapter 2 reviews computational workflows that reveal sequence-dependent conformations and supramolecular organization. Chapter 3 applies these principles to Dynamic Peptide Libraries which identify tetrapeptides that selectively interact with neurometabolites. Chapter 4 extends the same interaction-driven framework to design tryptophan-rich pentapeptides that co-assemble with kinase inhibitors …

Mapping Nucleosome Stability: Linking Oncogenic Structural Alterations To Long-Range Allosteric Communication, Augustine C. Onyema

Dissertations, Theses, and Capstone Projects

The nucleosome core particle (NCP) is essential for chromatin structure and function, serving as the fundamental unit of eukaryotic chromatin. Oncogenic mutations in core histones disrupt chromatin dynamics, altering DNA repair and transcription processes. How DNA communicates with histones, and how this information propagates through the histone, has been suggested to be a cooperative process. Here, I investigate the molecular consequences of two mutations, H2BE76K and H4R92T, using 36 µs of all-atom molecular dynamics simulations on Anton2. I also characterize the kinetic correlation within histone/DNA domains via conditional activity (CONDACT) using the dihedral angle as our degrees of …

Immunomodulatory And Signaling Molecules From Plant-Associated Bacteria: Toll-Like Receptor 4 Agonist Adjuvants And Diketopiperazine-Mediated Communication, Marian Romaine

Dissertations, Theses, and Capstone Projects

Medicinal plants and their associated microbiomes constitute a rich source of bioactive natural products with applications in immunotherapy and microbial ecology. Herbal formulations have long been valued for safe immune enhancement, while bacterial signaling molecules govern community behaviors critical to pathogenesis, symbiosis, and environmental processes. Bacterial lipopolysaccharides (LPS) from plant-associated Gram-negative bacteria have emerged as potent TLR4 agonists, yet their endotoxic potential limits direct use, and diketopiperazines (DKPs) serve as versatile quorum-sensing mediators capable of modulating biofilms in mixed microbial systems.

The work in this thesis comprises two independent but complementary research strands. The first strand pursued the engineering of …

Microtubules In Breast Cancer: Exploring The Α/Β-Tubulin Toggle Switch And Its Implications In Human Breast Cancer, Annemarie Ianos

Student Theses and Dissertations

Microtubules, composed of a/b-tubulin heterodimers, play a central role in breast cancer tumor growth by polymerizing, leading to metastasis and depolymerizing, contributing to proliferation. Human enzymes protein kinase Ca (PKC-a) and cyclin-dependent kinase 1 (Cdk-1) mediate phosphorylation at sites a:Ser165 and b:Ser172, respectively, influencing the growth of microtubules. It is possible that alternating phosphorylation at these sites contribute to an a/b-tubulin “toggle switch” that mediates microtubule instability and tumor growth.

The project investigates the influence of the toggle switch model on microtubule stability by determining the impact of mutants (a:S165D, a:S165N, a:S165S_P, b:S172S_P and a:S165S_P/b:S172S …

The Effects Of Cinnamaldehyde On Tetrahymena Thermophila, Sydney Kurland

Publications and Research

In addition to their common use as spices in cooking and baking, cinnamon plants, Cinnamomum zeylanicum and Cinnamomum cassia for example, have long been used in herbal remedies worldwide. Cinnamon contains many vital oils and active compounds including cinnamaldehyde (CMD). Numerous studies looking at potential therapeutic effects of cinnamon have demonstrated its antioxidant, anti-inflammatory, and antimicrobial properties (1, 2, 3).   Therefore, it is important to continue studying the efficacy, benefits, and mechanisms of action of cinnamon and CMD to have a complete understanding of its full potential. Tetrahymena thermophila is a ciliated protozoan commonly used as a model organism to …

Characterization And Advancement Of Molluscan Venom Gland Cell Model Systems, James V. Parziale

Dissertations, Theses, and Capstone Projects

Venomous mollusks, including cone snails and coleoid cephalopods, produce rich repertoires of bioactive peptides with profound effects on cellular physiology, yet there are few tractable experimental systems that exist to study their development, maintenance, and venom secretion. Although therapeutics such as the cone snail peptide Ziconotide demonstrate the biomedical potential of molluscan venoms, progress in understanding how venom glands form, function, and evolve has been hindered by the lack of reliable husbandry and the complete absence of in vitro cell models. Modern comparative genomics has revealed widespread convergent evolution across venomous lineages, but molluscan datasets remain underrepresented, limiting insights into …

Monosaccharide Binding To Synthetic Carbohydrate Receptor Microarrays, Milan A. Shlain

Dissertations, Theses, and Capstone Projects

Chapter 1: A glycan detection platform comprised of synthetic carbohydrate receptors (SCRs) immobilized onto polymer brushes was prepared. SCR043, an alkene-containing SCR, was incorporated into grafted-from polymer brushes using hypersurface photolithography, resulting in microarrays of SCR043-functionalized polymer brushes, where brush height (h) and SCR grafting density (Γ) is controlled precisely at each feature in the array. The influence of h and Γ on the binding to five fluorescently labelled monosaccharides – α-glucose (α-Gluc-FL), α-galactose (α-Gal-FL), α-mannose (α-Man-FL), β-glucose (β-Gluc-FL), and β-galactose (β-Gal-FL) – in aqueous buffer …

4e-Bp1 Differentially Regulates Translation Of A Subset Of Human Mrnas, Mehreen Mahbub

Dissertations, Theses, and Capstone Projects

Elevated levels of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) influence cap-independent translation by forming a complex with eukaryotic initiation factor 4E (eIF4E) (eIF4E•4E-BP1). Certain mRNAs—including those encoding hypoxia-inducible factor-1α (HIF-1α), fibroblast growth factor-9 (FGF-9), and two isoforms of tumor suppressors, p53 (p53_A, and p53_B)—contain structured 5’untranslated regions (UTRs) that enable translation either via cap-independent translation enhancer (CITE)-like or internal ribosomal entry site (IRES)-like mechanisms. However, how 4E-BP1 modulates these mechanisms remains unclear. Using fluorescence-based anisotropy assays, we showed that the eIF4E•4E-BP1 binds more tightly to the 5’ m⁷G-cap of these mRNAs than eIF4E …

Computational And Functional Characterization Of Terebrid Venom Peptides, Favour T. Achimba

Dissertations, Theses, and Capstone Projects

Venom peptides represent a natural repertoire of bioactive compounds that are potent modulators of ion channels. Teretoxins, venom peptides from terebrid snails, remain underexplored despite their structural and functional diversity. This thesis is the first to comprehensively explore the structure and function of teretoxins using a comparative computational sequence and structure model followed by experimental assays. The majority of the functional focus has been on identifying the ion channel molecular targets of uncharacterized teretoxins. Teretoxins, like other venom peptides, are hypothesized to manipulate the cellular function of a diversity of ion channels. Dysregulation of ion channels leads to several …

Protein Allostery Probed By Ligands Across Sites, Virgil A. Woods

Dissertations, Theses, and Capstone Projects

Allostery is a pervasive regulatory principle throughout biology, yet the structural pathways by which distal inputs alter active‑site chemistry within protein structures remain incompletely defined and exploited. This dissertation uses protein tyrosine phosphatase 1B (PTP1B) as a tractable model to map those pathways with complementary experimental and computational tools. I integrate high‑resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), room-temperature crystallography, NMR, steady-state kinetics, crystallographic pseudo-ensembles, and machine-learning-guided ligand discovery. The working premise is that regulation reflects redistribution within a conformational ensemble rather than a binary switch. That orthogonal perturbations by small molecules, mutations, and protein partners can be used to both …

Structural Characterization Of Peptide Nanoaggregates At Varying Concentrations And Their Impact On Cellular Responses, Malika Rozmetova

Theses and Dissertations

Peptide nano-assemblies can regulate cellular pathways in a structure-dependent manner. Here, we show that the enzyme-responsive peptide NapFFK(NBD)Yp forms distinct nanoscale assemblies at different concentrations, triggering differential ER stress and extracellular vesicle release in MDA-MB231 cells. These results highlight the importance of supramolecular organization in peptide–cell interactions.

Grapes Cure Cancer: My First Molecular Docking Analysis Of Resveratrol Binding To Anti-Apoptotic Protein Bcl-2: In Silico, Sydni Ann Kolokoltsev, Vishwas Joshi

Publications and Research

B-cell lymphoma 2 (BCL-2) is an anti-apoptotic protein frequently overexpressed in cancer, enabling tumor cells to evade programmed death. Resveratrol, a grape-derived polyphenol, has reported anticancer properties. Here we performed in silico docking of resveratrol to human BCL-2 using AutoDock Vina. The best-ranked pose exhibited a predicted binding free energy of 8.0 kcal/mol and formed at least one short hydrogen bond (~1.8 Å) with pocket residues. These results support further evaluation of resveratrol as a potential modulator of BCL-2-mediated apoptosis.

The Sonic Hedgehog Effector Smoothened Modulates Cholinergic Interneuron Activity, Physiology, And Striatum-Dependent Behaviors, Santiago Uribe-Cano

Dissertations, Theses, and Capstone Projects

The striatum is a central node in action selection and associative learning, integrating cortical, thalamic, and neuromodulatory input. Among its principal modulators, dopamine (DA) and acetylcholine (ACh) are known for their temporally coordinated yet mechanistically distinct influences on striatal output. However, the upstream signals that regulate their dynamic interplay, particularly within cholinergic interneurons (CINs)—the primary source of striatal ACh—remain incompletely characterized. This dissertation investigates the role of Smoothened (Smo), a G protein-coupled receptor (GPCR) effector of Sonic Hedgehog (Shh) signaling, in modulating ACh signaling dynamics in the striatum.

Building on evidence that midbrain DA neurons co-release Shh and that CINs …

Mechanistic Insights Into The Neuroprotective Effects Of The Antidepressant Agomelatine In Alzheimer's Disease, Grace Terry

Dissertations, Theses, and Capstone Projects

Alzheimer’s Disease (AD) is a complex neurodegenerative disease that has limited treatment options and no cure. AD is characterized by robust pathology including extracellular amyloid beta plaques, intracellular neurofibrillary tangles, neuronal and synaptic loss, neuroinflammation, and brain atrophy. AD presents with cognitive decline and memory loss but only years after neuropathology has started to accumulate. This robust pathology has made AD difficult to treat and highlights the need for therapeutics that modulate multiple pathways. Agomelatine (AGO) was selected by a high-throughput machine learning drug repurposing algorithm by our collaborator Dr. Lie Xie (Hunter College Dept. of Comp. Sci.) as having …

Investigating The Role Of Early Growth Response 1 (Egr1) Gene In Riluzole-Induced Apoptosis In Osteosarcoma, Syeda Maryam Azeem

Dissertations, Theses, and Capstone Projects

Osteosarcoma is a rare but aggressive bone malignancy most commonly affecting adolescents and young adults (AYA). With 5-year survival rate stagnating over the last four decades despite the advancements in multi-modal therapy, drug repurposing offers a rapid path to new osteosarcoma treatments. Recent studies suggest that Riluzole, a drug approved for amyotrophic lateral sclerosis (ALS), may be repurposed for osteosarcoma treatment due to its ability to slow tumor progression and induce apoptosis. Previously, we have shown that Riluzole increases reactive oxygen species (ROS), activating c-Abl, which phosphorylates YAP in the nucleus. YAP then forms a complex with p73 to enhance …

From Sequence To Allostery: How Amino Acid Differences Rewire Coupled Conformational Heterogeneity In The Ptp Enzyme Family, Shivani Sharma

Dissertations, Theses, and Capstone Projects

Protein Tyrosine Phosphatases (PTPs) are critical regulators of cellular signaling, and their activity is often modulated through allosteric mechanisms. Allostery is defined as a chemical or conformational change in one site of the protein due to a binding event at another site. Although several studies have investigated aspects of allostery in PTPs, the mechanistic foundations underlying allosteric regulation remain poorly understood. Despite a highly conserved catalytic domain across PTPs, regions with low or no conservation suggest potential "rewiring" of allosteric networks. This raises key questions about the universality versus individuality of allosteric mechanisms across the PTP family.

In this work, …

Exploring Variability Of The Cg18562578 Methylquant Assay For The Forensic Discrimination Of Monozygotic Twins, Sydney E. Arnold

Student Theses

Monozygotic (MZ) twins possess identical DNA sequences, posing a problem for forensic scientists, as they are incapable of distinguishing MZ twins from each other using traditional DNA identification methods. However, the epigenomes of MZ twins will differ and might be used for their forensic discrimination. Here, we explored the variability of an assay previously developed by our laboratory that showed high discrimination potential for MZ twins using buccal swab DNA, cg18562578 MethylQuant. We measured precision at each step: bisulfite conversion, nested PCR, and qPCR, reproducibility, and repeatability. DNA methylation ratios were compared between two analysts carrying each step using the …

Cg18562578 Methylquant Assay For The Discrimination Of Monozygotic Twins, Amber P. Chauca

Student Theses

Monozygotic (MZ) twins have identical DNA, making traditional profiling methods insufficient in their discrimination. However, MZ twins can be differentiated by their levels of DNA methylation. Our research group previously developed a methodology to detect cg18562578 DNA methylation levels in MZ twins based on a two- step PCR approach and a cg18562578 MethylQuant Assay. That study generated data for only 64% of the samples it investigated, and showed a discrimination power of 77% to discriminate between MZ twins. Here, we used the same methodology but a different approach to determine DNA methylation in 73 previously unsuccessful twin pairs. We diluted …

Elucidating The Roles Of Eukaryotic Initiation Factors Involved In Dap5 Mediated Translation, Jacob Nk Quartey

Dissertations, Theses, and Capstone Projects

Translation initiation in eukaryotes is a highly regulated process essential for accurate protein synthesis. It is a dynamic process that involves a complex interplay between messenger RNAs (mRNAs), ribosomal subunits, and a host of initiation factors, ensuring precise start codon selection and the subsequent assembly of the translation machinery. This process has well been known to be mediated by the eukaryotic Initiation Factor (eIF4F), which consists of the cap binding protein eIF4E, the scaffolding protein eIF4GI, and the helicase factor eIF4A.The recognition and binding of eIF4E to the m⁷G cap structure of the mRNA is essential for the …

Biophysical Analysis Of S100a12 And The Nucleosome Core Particle, Christopher Diforte Jr.

Dissertations, Theses, and Capstone Projects

Calcium signaling and chromatin remodeling are fundamental regulatory processes that control protein activity and gene expression, respectively. This thesis investigates the molecular mechanisms by which local ligand binding and structural perturbations propagate allosteric effects across larger protein systems, using two distinct yet mechanistically analogous models: the calcium binding protein S100A12 and the nucleosome core particle. These studies are unified by a shared emphasis on how physical forces govern biological function.

In the first part, we explore calcium mediated allostery in S100A12, focusing on the distinct roles of its two EF-hand calcium binding loops (EF-I and EF-II). Through a combination of …

Structural Studies Towards The Mechanism Of Scanning And Initiator Trna Recruitment During Eukaryotic Translation Initiation, Da Cui

Dissertations, Theses, and Capstone Projects

The central dogma, proposed by Francis Crick in 1958, marks the direction of the flow of genetic information: from DNA to DNA (DNA replication), DNA to RNA (transcription), and RNA to protein (translation). Each of these is tightly regulated and important for cells and organisms to function correctly, grow, and reproduce.

In the eukaryotic system, the initiation stage of translation is the first, the rate-limiting, and the most regulated stage. It involves direct regulation of multiple eukaryotic initiation factors (eIFs), scanning factors such as DHX29, and other factors such as Poly-A binding protein (PABP). It starts with the small subunit …

Characterization Of Sars-Cov-2 Replication And Transcription Complexes Via Structural And Evolutionary Approaches, Amelie Ghirardo, Ben Shabatian, Avishai Aghelian, Kyle Tau, Eleonora Gianti

Undergraduate Research

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused around 700M cases and over 7M COVID-19-related deaths recorded worldwide (World Health Organization, March 2025). Aiming to effectively combat this and other disease-causing Coronaviruses (CoV), unprecedented research efforts led to the development of new vaccines and antiviral therapies. Due to emergence of variants of concern (VOCs) with increased transmissibility, immune evasion from vaccination, and potential to resist the available treatments, SARS-CoV-2 continues to represent a major threat to global health. Hence, there is a pressing need to discover new antivirals with broad-spectrum efficacy against multiple SARS-CoV-2 variants and related CoVs. This project …

A Qualitative Nmr And Histological Analysis Of Adipocere Formation In Different Aqueous Environments Using Sus Scrofa Models, Mia M. Sorrentino

Student Theses

Adipocere is a wax-like crust that has the potential to form over corpses in moist, humid, and anaerobic environments, preserving them in a process similar to that of mummification. The substance can be identified within 3-6 months postmortem and is characterized by the ratio of saturated fatty acids to unsaturated fatty acids. Palmitic acid and stearic acid are the most abundant in comparison to myristic and oleic acids. The goal of this study was to investigate factors affecting adipocere formation in different aqueous environments. Pork belly samples were submerged in water samples collected from different places around New York City …

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …

Taming Biological Complexity Through The Use Of Symmetries, Luis A. Álvarez-García

Dissertations, Theses, and Capstone Projects

The study of biological systems is, inherently, the study of very complex systems. This is essentially due to the fact that they are made up of numerous, often very complicated, interactions between an extensive number of components. Often necessitating an abundance of quantitative parameters and details for a precise description. The human brain for ex- ample, consisting of ∼ 80 billion neurons with ∼ 800 to 100 trillion connections between them, each of them depending on a large set of parameters. Even simpler examples such as bacterial organisms, such as E. coli and B. subtilis, which we focus on …

Solvation Thermodynamic Mapping Approaches For Computer-Aided Drug Discovery, Vjay Molino

Dissertations, Theses, and Capstone Projects

The drug discovery process is inherently long and costly, prompting the development and integration of computational tools to mitigate these challenges. One of area explored in computer-aided drug discovery is to understand the role of solvation in protein-drug binding and to develop computational tools and methods that can be integrated in the drug discovery process. Grid Inhomogeneous Solvation Theory (GIST) is a tool that provides a framework for mapping solvation thermodynamiproperties of water molecules on the protein surface.This thesis explores the use of GIST in generating pharmacophore models and elucidates the role of solvation in protein structural fluctuations.

One of …

Optimizing Biofilm Assay Reproducibility And Characterizing The 12-Hydroxystearic Acid On Escherichia Coli, Khilola Khusanova

Theses and Dissertations

Biofilm formation in Escherichia coli plays a critical role in microbial chemical communication and surface-associated persistence. This study investigates the antibiofilm activity of 12-hydroxystearic acid (12-HSA), evaluating its R and S enantiomers as well as a racemic mixture. E. coli BL21, biofilms were grown under standardized laboratory conditions and quantified using the Crystal Violet staining assay. Treatment with 12-HSA resulted in a measurable reduction in biofilm biomass, with differences observed between the individual enantiomers and the mixture. These findings suggest that 12-HSA influences early adhesion and biofilm development, supporting its potential as a small-molecule modulator of bacterial surface behavior. This …