Digital Commons Network^™

Investigation Of Ai-2 Binding To The Quorum Sensing Receptor Lsrb, Meghann R. Kasal , '17

Senior Theses, Projects, and Awards

Bacterial cell-cell communication, known as quorum sensing, is a density-dependent phenomenon that regulates multicellular behaviors such as bioluminescence and virulence. Interspecies quorum sensing is mediated by a signal known as autoinducer-2 (AI-2), which belongs to a family of molecules derived from 4,5-Dihydroxy-2,3 pentanedione (DPD), a key metabolic product of the enzyme LuxS. AI-2 is recognized by many bacteria that belong to several phyla, including Enterobacteriaceae, Rhizobiaceae, and Bacillaceae, as a non-borated cyclic derivative of DPD known as (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran (R-THMF). Building on previous research, we have recently identified several novel LsrB orthologs through sequence alignments and fold-prediction software. …

Conformational Studies Of A Domain Of The Influenza A M2 Protein Involved In Viral Budding And Morphology, Alice L. Herneisen , '17

Senior Theses, Projects, and Awards

In my two years working in the Howard lab, I have cycled through a number of projects. These projects fall under the broad context of studying of how the cytoplasmic tail of a particular membrane protein of the influenza A virus, the Matrix protein 2 (M2), is involved in viral budding. I have chosen to present each project in the form of an independent manuscript, with separate Introduction, Experimental, Results, and Discussion sections. Some broader background and theory is briefly provided in Chapters 1 and 2, but Chapters 3-5 are designed to be largely self-contained. Potential future directions pertaining to …

Multi-Scaled Approaches For Protecting Montana's Watersheds And Water Resources, Elizabeth Yoder

Graduate Student Portfolios, Professional Papers, and Capstone Projects

The central theme carried among my four portfolio pieces is: using scientific and governmental approaches to conserve watershed health. For the purposes of this portfolio, I define watershed health as a very general term that describes the state of water quantity and quality that is available for human and ecosystem needs in a watershed. I see each of my portfolio pieces focusing on a different scale and method (i.e., science or government, including different levels of government, local, state and federal) for conserving watershed health. My first portfolio piece reviews water quality degradation caused by pharmaceuticals and personal care products …

Integrating The Field Of Prebiotic Chemistry Into A Christian Worldview, Matthew B. Anderson

Senior Honors Theses

This thesis will provide an overarching examination into the scientific field of prebiotic chemistry, the purported chemistry of the formation of life on earth. Prebiotic chemistry is a critical area of science particularly for Christian scientists to study since it is used by many evolutionists as evidence for the evolution of life, rather than the formation by an intelligent designer. Extensive literature-based research from previously published articles will be conducted on the formation of biologically necessary molecules, including amino acids. Primary focus will be placed on the formation of amino acids in a primordial earth environment, first demonstrated by the …

Mmtv-Pymt And Derived Met-1 Mouse Mammary Tumor Cells As Models For Studying The Role Of The Androgen Receptor In Triple-Negative Breast Cancer Progression, Jessica L. Christenson, Kiel T. Butterfield, Nicole S. Spoelstra, John D. Norris, Jatinder S. Josan, Julie A. Pollock, Donald P. Mcdonnell, Benita S. Katzenellenbogen, John A. Katzenellenbogen, Jennifer K. Richer

Chemistry Faculty Publications

Triple-negative breast cancer (TNBC) has a faster rate of metastasis compared to other breast cancer subtypes and no effective targeted therapies are currently FDA-approved. Recent data indicate that the androgen receptor (AR) promotes tumor survival and may serve as a potential therapeutic target in TNBC. Studies of AR in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an AR-positive (AR+) immunocompetent preclinical model. In this study we identified the transgenic MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor antigen) mouse mammary gland carcinoma model of breast cancer and Met-1 cells derived from this model …

Microbial Degradation Of Various Organic Pollutants Using Bacteria Isolated From Petroleum Sludge, Manal Ali Alhefeiti

Theses

Intensification of agriculture and manufacturing industries has resulted in increased release of a wide range of xenobiotic compounds to the environment. The extensive discharge of hazardous waste in industrial wastewater and the recalcitrant nature of some of these organic pollutants have fueled a strong interest in exploring efficient and environmentally friendly approaches for wastewater remediation. Bioremediation approaches can provide efficient, inexpensive and environmentally safe cleanup tools. In the present study, our main objective was to isolate novel bacterial strains from UAE petroleum sludge and to examine their abilities to degrade various aromatic pollutants, including azo dyes and emerging pollutants. We …

Quef-Like, A Non-Homologous Archaeosine Synthase From The Crenarchaeota, Adriana Bon Ramos, Lide Bao, Ben Turner, Valérie De Crécy-Lagard, Dirk Iwata-Reuyl

Chemistry Faculty Publications and Presentations

Archaeosine (G+) is a structurally complex modified nucleoside ubiquitous to the Archaea, where it is found in the D-loop of virtually all archaeal transfer RNA (tRNA). Its unique structure, which includes a formamidine group that carries a formal positive charge, and location in the tRNA, led to the proposal that it serves a key role in stabilizing tRNA structure. Although G+ is limited to the Archaea, it is structurally related to the bacterial modified nucleoside queuosine, and the two share homologous enzymes for the early steps of their biosynthesis. In the Euryarchaeota, the last step of the archaeosine biosynthetic pathway …

Prevention And Reversal Of Selenite-Induced Cataracts By N-Acetylcysteine Amide In Wistar Rats, Yasaswi Maddirala, Shakila Tobwala, Humeyra Karacal, Nuran Ercal

Chemistry Faculty Research & Creative Works

Background: The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups.

Methods: Forty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups …

Reactivity Of Ketyl And Acetyl Radicals From Direct Solar Actinic Photolysis Of Aqueous Pyruvic Acid, Alexis J. Eugene, Marcelo I. Guzman

Chemistry Faculty Publications

The variable composition of secondary organic aerosols (SOA) contributes to the large uncertainty for predicting radiative forcing. A better understanding of the reaction mechanisms leading to aerosol formation such as for the photochemical reaction of aqueous pyruvic acid (PA) at λ ≥ 305 nm can contribute to constrain these uncertainties. Herein, the photochemistry of aqueous PA (5-300 mM) continuously sparged with air is re-examined in the laboratory under comparable irradiance at 38° N at noon on a summer day. Several analytical methods are employed to monitor the time series of the reaction, including (1) the derivatization of carbonyl (C═O) functional …

Topological And Thermodynamic Factors That Influence The Evolution Of Small Networks Of Catalytic Rna Species, Jessica Anne Mellor Yeates, Philippe Nghe, Niles Lehman

Chemistry Faculty Publications and Presentations

An RNA-directed recombination reaction can result in a network of interacting RNA species. It is now becoming increasingly apparent that such networks could have been an important feature of the RNA world during the nascent evolution of life on the Earth. However, the means by which such small RNA networks assimilate other available genotypes in the environment to grow and evolve into the more complex networks that are thought to have existed in the prebiotic milieu are not known. Here, we used the ability of fragments of the Azoarcus group I intron ribozyme to covalently self-assemble via genotype-selfish and genotype-cooperative …

Comparative Analysis Of Antihistamines And Nonsteroidal Anti-Inflammatory Drugs (Nsaids): Properties, Structure And Prediction Of New Potential Drugs, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To determine the molecular properties of common antihistamines and non-steroidal antiinflammatory agents (NSAIDs). To identify interrelationships among these two groups of drugs utilizing pattern recognition methods and statistical analysis.

Study Design: After determination of molecular properties, values thereof are examined using pattern recognition methods and other numerical analysis for underlying relationships and similarities.

Place and Duration of Study: Durham Science Center, University of Nebraska, Omaha, Nebraska from September 2016 to January 2017.

Methodology: Thirty compounds were identified as antihistamines and 27 compounds identified as NSAIDs. Properties such as Log P, molecular weight, polar surface area, etc. are determined. Molecular …

Plp And Gaba Trigger Gabr-Mediated Transcription Regulation In Bacillus Subtilis Via External Aldimine Formation, Rui Wu, Ruslan Sanishvili, Boris R. Belitsky, Jose I. Juncosa, Hoang V. Le, Helaina J. S. Lehrer, Michael Farley, Richard B. Silverman, Gregory A. Petsko, Dagmar Ringe, Dali Liu

Chemistry: Faculty Publications and Other Works

The Bacillus subtilis protein regulator of the gabTD operon and its own gene (GabR) is a transcriptional activator that regulates transcription of γ-aminobutyric acid aminotransferase (GABA-AT; GabT) upon interactions with pyridoxal-5′-phosphate (PLP) and GABA, and thereby promotes the biosynthesis of glutamate from GABA. We show here that the external aldimine formed between PLP and GABA is apparently responsible for triggering the GabR-mediated transcription activation. Details of the “active site” in the structure of the GabR effector-binding/oligomerization (Eb/O) domain suggest that binding a monocarboxylic γ-amino acid such as GABA should be preferred over dicarboxylic acid ligands. A reactive GABA analog, ( …

Photochemical Properties And Structure-Activity Relationships Of RuIi Complexes With Pyridylbenzazole Ligands As Promising Anticancer Agents, Dmytro Havrylyuk, David K. Heidary, Leona Nease, Sean Parkin, Edith C. Glazer

Chemistry Faculty Publications

Ruthenium complexes capable of light‐triggered cytotoxicity are appealing potential prodrugs for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT). Two groups of (polypyridyl)Ru^II complexes with 2‐(2‐pyridyl)benzazole ligands were synthesized and investigated for their photochemical properties and anticancer activity to compare strained and unstrained systems that are likely to have different biological mechanisms of action. The structure–activity relationship was focused on the benzazole‐core bioisosterism and replacement of coligands in Ru^II complexes. Strained compounds rapidly ejected the 2‐(2‐pyridyl)benzazole ligand after light irradiation, and possessed strong toxicity in the HL‐60 cell line both under dark and light conditions. In contrast, unstrained Ru …

Angiotensin Receptor Blocker Drugs And Inhibition Of Adrenal Beta-Arrestin-1-Dependent Aldosterone Production: Implications For Heart Failure Therapy, Anastasios Lymperopoulos, Beatrix Aukszi

Chemistry and Physics Faculty Articles

Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II (AngII). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure (HF), is induced by AngII type 1 receptors (AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1 (βarr1) or -2 (βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 protein-independent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that …

Hydrogen Peroxide Inhibition And Inactivation Of Bicupin Oxalate Oxidase, John M. Goodwin Vii

Master of Science in Chemical Sciences Theses

Oxalate oxidase is a manganese containing enzyme that catalyzes the oxygen dependent oxidation of oxalate to carbon dioxide and hydrogen peroxide. Oxalate oxidase from Ceriporiopsis subvermispora (CsOxOx) is the first characterized bicupin oxalate oxidase. Potential applications of oxalate oxidase in cancer treatment, paper pulping, and biofuel cells highlight the need to study the effects of hydrogen peroxide on the CsOxOx catalyzed oxidation of oxalate. Membrane inlet mass spectrometry (MIMS) was used to directly measure initial rates of carbon dioxide formation and oxygen consumption in varying initial concentrations of hydrogen peroxide. This work demonstrates that hydrogen peroxide is both a reversible …

Hierarchical Corannulene-Based Materials: Energy Transfer And Solid-State Photophysics, Allison M. Rice, W. Brett Fellows, Ekaterina A. Dolgopolova, Andrew B. Greytak, Aaron K. Vannucci, Mark D. Smith, Stavros G. Karakalos, Jeanette A. Krause, Stanislav M. Avdoshenko, Alexey A. Popov, Natalia B. Shustova Prof. Dr.

Faculty Publications

We report the first example of a donor–acceptor corannulene-containing hybrid material with rapid ligand-to-ligand energy transfer (ET). Additionally, we provide the first time-resolved photoluminescence (PL) data for any corannulene-based compounds in the solid state. Comprehensive analysis of PL data in combination with theoretical calculations of donor–acceptor exciton coupling was employed to estimate ET rate and efficiency in the prepared material. The ligand-to-ligand ET rate calculated using two models is comparable with that observed in fullerene-containing materials, which are generally considered for molecular electronics development. Thus, the presented studies not only demonstrate the possibility of merging the intrinsic properties of π-bowls, …

Uv-Vis And Fluorescence Studies Of Zinc Enzyme Active Site Mimics And Their Binding Of Inhibitor Compounds, Aeshah Hussain Niyazi

College of Science and Health Theses and Dissertations

This research aimed to synthesize and characterize Zn2+-ligand complexes that have the same zinc coordination environment as in histone deacetylase (HDAC) and other important zincdependent enzymes. Mimicking the structural and the functional properties of Zn2+-enzymes will allow us to understand the binding reactivity between Zn2+ and small molecule enzyme inhibitors. The new understanding will help to develop new approaches to target disease states such as cancer. A variety of Zn2+ binary complexes have been synthesized and their interactions with inhibitors such as suberanilohydroxamic acid (SAHA) and 8-Hydroxyquinoline (8HQ) have been studied using 1H NMR, UV-Vis, and fluorescence spectroscopies. Attempts were …

Calmodulin Lobes Facilitate Dimerization And Activation Of Estrogen Receptor-Alpha, Zhigang Li, Yonghong Zhang, Andrew C. Hedman, James B. Ames, David B. Sacks

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Estrogen receptor α (ER-α) is a nuclear hormone receptor that controls selected genes, thereby regulating proliferation and differentiation of target tissues, such as breast. Gene expression controlled by ER-α is modulated by Ca²⁺ via calmodulin (CaM). Here we present the NMR structure of Ca²⁺-CaM bound to two molecules of ER-α (residues 287–305). The two lobes of CaM bind to the same site on two separate ER-α molecules (residues 292, 296, 299, 302, and 303), which explains why CaM binds two molecules of ER-α in a 1:2 complex and stabilizes ER-α dimerization. Exposed glutamate residues in CaM (Glu-11, …

Calmodulin Lobes Facilitate Dimerization And Activation Of Estrogen Receptor-Α, Zhigang Li, Yonghong Zhang, Andrew C. Hedman, James B. Ames, David B. Sacks

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Estrogen receptor α (ER-α) is a nuclear hormone receptor that controls selected genes, thereby regulating proliferation and differentiation of target tissues, such as breast. Gene expression controlled by ER-α is modulated by Ca2+ via calmodulin (CaM). Here we present the NMR structure of Ca2+-CaM bound to two molecules of ER-α (residues 287–305). The two lobes of CaM bind to the same site on two separate ER-α molecules (residues 292, 296, 299, 302, and 303), which explains why CaM binds two molecules of ER-α in a 1:2 complex and stabilizes ER-α dimerization. Exposed glutamate residues in CaM (Glu-11, Glu-14, Glu-84, …

Cytotoxic And Antimicrobial Effects Of Silver-Containing Surfaces, Sarah Goderecci

Theses and Dissertations

This study examines applications of sputtered silver coatings as alternatives to traditional antibiotic treatments. Given the increase in reports of antibiotic-resistant bacteria, new treatments and coatings for in-dwelling medical devices such as catheters and orthopedic implants are necessary. Silver oxide films were deposited onto Ti surfaces to examine the efficacy of such coatings against a variety of bacterial species both in vitro and in vivo. Bacterial growth studies showed that coatings exhibited antimicrobial activity against a range of bacterial species acting either in a bacteriostatic or bactericidal mechanism, depending on the target. Limited toxicity to in vitro mammalian cells was …

Utilizing Phluorin-Tagged Receptors To Monitor Subcellular Localization And Trafficking, Ashley M. Fox-Loe, Brandon J. Henderson, Christopher I. Richards

Chemistry Faculty Publications

Understanding membrane protein trafficking, assembly, and expression requires an approach that differentiates between those residing in intracellular organelles and those localized on the plasma membrane. Traditional fluorescence-based measurements lack the capability to distinguish membrane proteins residing in different organelles. Cutting edge methodologies transcend traditional methods by coupling pH-sensitive fluorophores with total internal reflection fluorescence microscopy (TIRFM). TIRF illumination excites the sample up to approximately 150 nm from the glass-sample interface, thus decreasing background, increasing the signal to noise ratio, and enhancing resolution. The excitation volume in TIRFM encompasses the plasma membrane and nearby organelles such as the peripheral ER. Superecliptic …

Analysis And Control Of Chain Mobility In Protein Hydrogels, Peter B. Rapp, Ahmad K. Omar, Jeff J. Shen, Maren E. Buck, Zhen Gang Wang, David A. Tirrell

Chemistry: Faculty Publications

Coiled-coil domains can direct the assembly of protein block copolymers into physically cross-linked, viscoelastic hydrogels. Here, we describe the use of fluorescence recovery after photobleaching (FRAP) to probe chain mobility in reversible hydrogels assembled from engineered proteins bearing terminal coiled-coil domains. We show that chain mobility can be related to the underlying dynamics of the coiled-coil domains by application of a three-state “hopping” model of chain migration. We further show that genetic programming allows the effective mobility of network chains to be varied 500-fold through modest changes in protein sequence. Destabilization of the coiled-coil domains by site-directed mutagenesis increases the …

Eco-Friendly (Green) Synthesis Of Magnetically Active Gold Nanoclusters, Naveen Reddy Kadasala, Lu Lin, Christopher Gilpin, Alexander Wei

Department of Chemistry Faculty Publications

Au–FexOy composite nanoparticles (NPs) are of great technological interest due to their combined optical and magnetic properties. However, typical syntheses are neither simple nor ecologically friendly, creating a challenging situation for process scale-up. Here we describe conditions for preparing Au–FexOy NPs in aqueous solutions and at ambient temperatures, without resorting to solvents or amphiphilic surfactants with poor sustainability profiles. These magnetic gold nanoclusters (MGNCs) are prepared in practical yields with average sizes slightly below 100 nm, and surface plasmon resonances that extend to near-infrared wavelengths, and sufficient magnetic moment (up to 6 emu g–1) to permit collection within minutes by …

Ice Cloud Formation Potential By Free Tropospheric Particles From Long-Range Transport Over The Northern Atlantic Ocean, Swarup China, Peter A. Alpert, B. Zhang, Simeon Schum, Katja Dzepina, Kendra Wright, R. Chris Owen, Paulo Fialho, Lynn Mazzoleni, Claudio Mazzoleni, Daniel A. Knopf

Department of Chemistry Publications

Long-range transported free tropospheric particles can play a significant role on heterogeneous ice nucleation. Using optical and electron microscopy we examine the physicochemical characteristics of ice nucleating particles (INPs). Particles were collected on substrates from the free troposphere at the remote Pico Mountain Observatory in the Azores Islands, after long-range transport and aging over the Atlantic Ocean. We investigate four specific events to study the ice formation potential by the collected particles with different ages and transport patterns. We use single-particle analysis, as well as bulk analysis to characterize particle populations. Both analyses show substantial differences in particle composition between …

Comparison Of Halide Receptors Based On H, Halogen, Chalogen, Pnicogen, And Tetrel Bonds, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

A series of halide receptors are constructed and the geometries and energetics of their binding to F-, Cl-, and Br- assessed by quantum calculations. The dicationic receptors are based on a pair of imidazolium units, connected via a benzene spacer. The imidazoliums each donate a proton to a halide in a pair of H-bonds. Replacement of the two bonding protons by Br leads to binding via a pair of halogen bonds. Likewise, chalcogen, pnicogen, and tetrel bonds occur when the protons are replaced, respectively, by Se, As, and Ge. Regardless of the binding group considered, F- is bound much more …

Formation, Characterization, And Optimization Of Antibody-Gold Nanoparticle Conjugates, Seth L. Filbrun

Theses and Dissertations

Protein modified gold nanoparticle based immunoassays are the basis of many novel detection techniques. There are many groups working on novel immunoassays but there is still much to understand about how many proteins are attached onto each nanoparticle and much to improve on immobilization methods. This thesis work is devoted to improving techniques for the quantification of protein immobilized on the gold nanoparticle and development of a novel approach to immobilize protein independent of pH.

The ability to evaluate antibody immobilization onto gold nanoparticles is critical for assessing coupling chemistry and optimizing the sensitivity of nanoparticle-enabled biosensors. Herein, we developed …

Polymer Micelle Formulation For The Proteasome Inhibitor Drug Carfilzomib: Anticancer Efficacy And Pharmacokinetic Studies In Mice, Ji Eun Park, Se-Eun Chun, Derek Alexander Reichel, Jee Sun Min, Su-Chan Lee, Songhee Han, Gongmi Ryoo, Yunseok Oh, Shin-Hyung Park, Heon-Min Ryu, Kyung Bo Kim, Ho-Young Lee, Soo Kyung Bae, Younsoo Bae, Wooin Lee

Pharmaceutical Sciences Faculty Publications

Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradable block copolymers poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) can improve the metabolic stability of CFZ in vitro. Here, we prepared the CFZ-loaded PM, PEG-PCL-deoxycholic …

Ten-Year Chemical Signatures Associated With Long-Range Transport Observed In The Free Troposphere Over The Central North Atlantic, B. Zhang, R. C. Owen, Judith Perlinger, D. Helmig, M. Val Martín, L. Kramer, Lynn Mazzoleni, C. Mazzoleni

Department of Chemistry Publications

Ten-year observations of trace gases at Pico Mountain Observatory (PMO), a free troposphere site in the central North Atlantic, were classified by transport patterns using the Lagrangian particle dispersion model, FLEXPART. The classification enabled identifying trace gas mixing ratios associated with background air and long- range transport of continental emissions, which were defined as chemical signatures. Comparison between the chemical signatures revealed the impacts of natural and anthropogenic sources, as well as chemical and physical processes during long transport, on air composition in the remote North Atlantic. Transport of North American anthropogenic emissions (NA-Anthro) and summertime wildfire plumes (Fire) significantly …

Synthesis Of Small Molecule Anti-Trypanosomal Drugs, Samuel Anderson

UNO Student Research and Creative Activity Fair

Demand for novel chemotherapeutic agents that treat Human African Trypanosomaiasis (HAT) persists. A series of compounds sharing a 3,4’diphephyl ether skeleton were prepared for a structure activity relationship (SAR) study evaluating antitrypansomal drug candidates. Trypanocidal assays performed in vitro by the Swiss Tropical and Public Health Institute identified a lead with an IC50 of 1.35 μg/mL analogous to a compound previously made in our laboratory. A slight improvement in activity (10%) was observed when changing the molecular substitution pattern from 4,4’ to 3,3’; however, the result is equivocal. Furthermore, in vitro test results demonstrated the weakness of amides as side …

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch

UNO Student Research and Creative Activity Fair

Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: …