| Willow C. Reese | MG 2001 | 8:30 | Computational analysis of the Factor V Leiden mutation and binding differences with Activated Protein C | Factor V Leiden is a blood disorder characterized by excessive clotting caused by a point mutation in the gene coding for residue 506R of the Factor V protein (FacV). FacV Leiden is the leading cause of inherited thrombophilia, affecting 5% of caucasian people and 1 in 50 people of African or Hispanic descent. This excessive clotting is due to an inability of the mutated FacV protein to bind with Activated Protein C (APC) and Protein S (PS), regulatory proteins that bind to the FacV protein, deactivating it and preventing initiation of the coagulation cascade. Through computational methods, such as HADDOCK docking and Amber Molecular Dynamics, this project seeks to characterize the binding between FacV and APC to better understand the specific chemistry preventing FacV deactivation. This work will lay the foundations of future research in pharmaceutical development, allowing for different compounds to be identified to treat or cure this disorder. |
| Dagmawit Kebede | MG 1098 | 9:00 | Allosteric inhibition of Matrix Metalloproteinase 9 (MMP-9) in silico as a potential cancer therapeutic | Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that promotes tumor invasion, metastasis, and angiogenesis through extracellular matrix degradation, making it an important therapeutic target in cancer. Traditional inhibitors target the catalytic Zn²? site, but this region is highly conserved among metalloproteinases, often leading to poor selectivity and side effects. Allosteric inhibition provides an alternative strategy by targeting distal binding pockets to modulate enzyme activity without directly interacting with the catalytic zinc site. In this study, the FTMap server was used to identify potential allosteric hotspots on MMP-9. Ligands were generated and docked using DOCK6. From these, 157 top-scoring complexes were selected for 250 ns molecular dynamics simulations in AMBER, and binding stability was evaluated using Molecular Mechanics Generalized Born Surface Area (MM-GBSA) free energy calculations. Several ligands showed stable interactions within the predicted allosteric pocket, supporting the feasibility of selectively targeting allosteric sites in MMP-9 for inhibitor development. |
| Audrey Brown | MG 1098 | 9:15 | Computational Analysis of Factor V Leiden: APC and Protein S Interactions | Factor V (FV) is a key regulatory protein in the coagulation cascade. FV remains inactive until thrombin converts it into active Factor Va (FVa). Under normal conditions, clotting is regulated by the activated protein C and protein S (APC:PS) complex, which inactivates FVa. However, in Factor V Leiden (FVL), a single point mutation disrupts the APC:PS deactivation and increases the risk of abnormal clotting. Currently, no specific cure exists for FVL. Molecular modeling was performed to characterize the stability of APC and PS, as well as the specific binding interactions within the APC:PS complex. Molecular dynamics simulations (1000 ns, triplicate) and analysis for stability and conformational dynamics of APC, PS, and the APC:PS complex. Preliminary results indicate favorable binding of APC:PS, supporting their integral role in FVa regulation. These results provide insight into how the APC:PS complex deactivates blood clotting. |
| Abbie A. Wigger | MG 1098 | 9:30 | Computational Analysis of Amyloid-Beta Disaggregation Using Polyphenol Ligands | Alzheimer’s disease (AD) is a neurodegenerative disease that destroys necessary mental functions and is one of the leading causes of death in America for individuals over the age of 65. A hallmark trait of AD is the aggregation of amyloid-β peptides forming plaques in the brain. There are currently no cures or effective treatments for AD. Polyphenol ligands have shown promise in the inhibition of amyloid-β plaque formation. To test this proposed inhibition, computational biochemical methods were used to gain insight into the effects of polyphenol ligands, namely piceatannol (PCT) and pinosylvin (PNO), on the disaggregation of amyloid-β plaques. Our simulations revealed that both PCT and PNO disrupt the amyloid-β protein to varying degrees. Our results help advance the theory of polyphenol drugs as potential inhibitors for the aggregation of the amyloid-β protein. |
| Isabelle M. Zagarri | MG 1098 | 10:15 | A computational study of the Factor V Leiden mutation and its effect on blood coagulation | Factor V (FV) is a critical blood-clotting protein of the coagulation system. This inactive form circulates the blood stream until needed, then is activated to Factor Va (FVa) by thrombin. FVa can be deactivated by a complex of activated protein C and protein S (APC:PS), inhibiting the coagulation cascade. A single amino acid mutation from an arginine to a glutamine at residue 506 causes Factor V Leiden (FVL), which impairs the binding of APC:PS to FVa, increasing the likelihood of abnormal blood clots. There is no cure for this mutation – only anticoagulant drugs are prescribed. Using computational methods, we observe binding interactions between FVa and APC. Results show that the Leiden mutant forms a less stable complex with APC than it does with the wild type. Future work includes simulating and analyzing FVa:APC:PS and FVL:APC:PS, and determining the important amino acid binding sites. |
| Alicia M. Jorgensen | MG 1000 | 10:45 | Testing Cyclophilin Dependent Lifespan Extension in Drosophila | Every organism has a lifespan that is shortened by disease and aging. A longer life with meaningful experiences is a goal of many. Work in mice indicates that mutations affecting Cyclophilin D (CypD), which block cell death, can slightly extend lifespan. The fruit fly Drosophila is helping address the cellular/molecular mechanisms of lifespan extension due to their genetic similarity to humans, their fully sequenced genome, genetic toolkit, and short lifespan. The Cyclophilin 1 (Cyp1) gene/protein may also be the fly version of CypD. We are therefore examining how Cyp1 mutations influence lifespan. Two Cyp1 insertion mutants do not extend lifespan, though these mutants show mild defects in a larval crawling assay. RNA interference knockdowns of Cyp1 have stronger phenotypes and may live longer as adult flies, though data collection continues. If the strong knockdown data remains consistent, our studies may establish a new, druggable, mechanism for extending lifespan. |
| Kaiden Zaborowski | MG 1098 | 10:45 | Computational investigation of the Human γS-crystallin protein associated with cataracts formation | Using computational methods the human γS-crystallin dimer (PDB: 6FD8) was investigated. Dimerization of this protein occurs via an intermolecular disulfide bond at Cys24 leading to a biphasic unfolding and a high aggregation propensity in the aging lens. To begin the computational investigation, 500 ns Molecular Dynamics (MD) simulations were conducted in triplicate to evaluate the structural stability of the dimer. Then 500ns Constant pH Molecular Dynamics (CpHMD) simulations were implemented to identify the protonation states of essential aspartate residues acting as hydrogen donors near the disulfide bond. Finally, Dock6 was utilized to model the binding mechanisms of Dithiothreitol (DTT) to the γS-crystallin dimer, exploring its efficacy as a reducing agent to break the pathogenic disulfide bond. By integrating MD, cpHMD, and docking protocols, this study elucidates the dimer’s stability and provides a foundation for developing therapeutic ligands to combat oxidative protein damage within the eye lens. |
| Aleece Walker | MG 1000 | 11:00 | Cyclophilin 1 mutations alter Drosophila larval crawling | Drosophila larvae crawl via peristalsis, a wave of muscle contraction that moves from posterior to anterior. The reverse occurs during backward locomotion. Crawling is interrupted when larvae search, pausing to swing their head and choose a new direction. Cyclophilin 1 (Cyp1) may be a mitochondrial protein that regulates cell death and cell signaling. Searching behavior and backward crawling are increased when Cyp1 is knocked down in either all neurons or all glial cells. The neural circuitry for searching behavior is unknown. Glia help to establish neural circuits during embryonic development and modulate circuit activity in the mature CNS. Because glia contribute to both neural circuit development and function, we are attempting to identify when Cyp1 is required in glia for normal crawling behavior. While we don’t know if this crawling defect comes from cell death or altered signaling, this work reflects how mitochondria can influence animal behavior. |
| Haleluya T. Merga | MG 1000 | 13:00 | Computational inhibition of Matrix metalloproteinase 9 (MMP-9) as potential cancer therapeutics | Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase involved in tissue remodeling, wound healing, and neuroplasticity. Although important in normal physiology, overexpression of MMP-9 promotes extracellular matrix degradation and contributes to cancer invasion and metastasis. Developing selective inhibitors has been difficult because of high structural similarity between MMP-9 and MMP-2, which has led to off-target inhibition. Generic de novo design method was used to generate 397 candidate inhibitors. All candidates were docked into the catalytic domain of MMP-9 using DOCK6, with the catalytic Zn2+ ion included in the docking model. Top-ranked ligands, along with the control inhibitor batimastat (BB-94), were further evaluated by molecular dynamics simulations using AMBER, followed by binding free energy analysis. Several candidates maintained stable interactions with the catalytic zinc ion and showed favorable binding throughout the simulations. Comparative analysis with MMP-2 also suggested greater binding preference for MMP-9, supporting their potential as lead compounds for cancer therapeutics. |
| Dagmawit Kebede | MG 1098 | 13:15 | Developing novel inhibitors for Striatal-Enriched Tyrosine Phosphatase (STEP) using computational methods | Striatal-Enriched Tyrosine Phosphatase (STEP) is a brain-specific phosphatase that negatively regulates synaptic signaling by dephosphorylating neuronal substrates. Overactivation of STEP has been linked to neurological disorders, including Alzheimer’s disease and schizophrenia, making it a promising therapeutic target. Although TC-2153 is a known STEP inhibitor, its high cost and limited accessibility highlight the need for alternative compounds. In this study, computational screening and simulation were used to identify potential STEP inhibitors. Approximately 2.5 million ligands from the ZINC database were screened against STEP using AutoDock Vina, while de novo ligands were generated and docked with DOCK6, including ongoing efforts to identify potential allosteric binding sites. Top candidates were evaluated using 250 ns molecular dynamics simulations in AMBER and binding free energies were estimated using Molecular Mechanics Generalized Born Surface Area (MM-GBSA) calculations. Several ligands showed stronger predicted binding energies than TC-2153, suggesting promising scaffolds for future STEP inhibitor development. |
| Suhani B. Patel | MG 1000 | 13:45 | Computational Investigation of Positive Cooperativity in the cMyb-KIX-MLL Ternary Complex | The KIX domain of the CREB-binding protein (CBP) behaves as a transcriptional coactivator, mediating interactions of multiple transcription factors, including c-Myb and the mixed lineage leukemia protein (MLL). c-Myb plays a critical role in the proliferation and differentiation of hematopoietic cells. Experimental and computational studies have shown the binding of MLL to KIX increases the affinity of c-Myb. This results in a positively cooperative ternary complex through an allosteric mechanism, which is important in transcription regulation. An overexpression of c-Myb has been linked to cancer, especially acute myeloid leukemia (AML). In this study, computational chemistry methods were used to investigate the structural basis of this cooperativity, and identify potential small-molecule inhibitors targeting the c-Myb-KIX binding pocket. Drug-like compounds from the ZINC20 database were screened using molecular docking. Promising candidates were further evaluated using molecular dynamics simulations with the AMBER to assess binding stability and conformational effects on the KIX domain. |
| Sofia Kattentidt, Ashelynn Courtney, Alex Kepes, and Laura Varo | Activities Room | 14:30 | How Protective is Your Toothpaste? An Ion-Selective Electrode Approach to Determining Fluoride Content in Toothpaste | Fluoride is a key ingredient in toothpaste, contributing to enamel remineralization and the prevention of dental cavities. This study aims to quantify fluoride concentrations in three commercially available and marketed as “protective” toothpastes: Sensodyne Repair and Protect, Crest Plus Cavity Protection, and Colgate Total Active Protection. Fluoride ion-selective electrode (ISE) analysis will be used to measure aqueous free fluoride, while spiked blanks and samples will evaluate method accuracy. Calibration curves generated from the fluoride standards will allow conversion of electrode potentials to fluoride concentration. The results will help assess the consistency of labeled fluoride content across brands and answer the question of whether these toothpastes are actually protective, based on the amount of fluoride found. |
| Makda Gebreegziabher | Activities Room | 14:30 | Computational Design of Matrix Metalloproteinase-9 (MMP-9) Inhibitors as Potential Cancer Therapeutics | Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent protein involved in extracellular matrix (ECM) breakdown leading to biological processes such as tissue remodeling and wound healing. In cancer, MMP-9 promotes tumor invasion and metastasis through excessive ECM degradation. However, due to its high homology with other MMPs, especially MMP-2, inhibitors like BB-94 failed clinically because of poor selectivity and off-target effects. To identify improved candidates, 397 compounds were generated from de novo drug design and 97 compounds were obtained from the PubChem database. Computational approaches including molecular docking, molecular dynamics simulations and binding free energy calculations were used to evaluate these potential compounds. The current top inhibitor showed a more favorable binding to MMP-9 than the control inhibitor, BB-94. Our results suggest several candidates for selective MMP-9 inhibition that could potentially lead to advances in cancer treatment. Other works include using alternate methods to identify improved compounds and testing their selectivity. |
| Allison Gibson, Briggs Maynor, and Chris Beersman | Activities Room | 14:30 | Determination of Trace Metal Concentration in Kirksville Water | The Environmental Protection Agency, Missouri Department of Natural Resources, and Missouri Department of Health all set standards for trace metal concentration in water supplies. Metal concentrations of arsenic, copper, lead, manganese, and molybdenum in water were analyzed from various sources of water in Adair County. This was done by collecting water samples from Forest Lake, Hazel Creek Lake, Bear Creek, Magruder Hall, Ryle Hall, Apartment A on the west side of Truman State University, and Apartment B on the east side of Truman State University. The metal concentrations were then quantized through graphite furnace atomic absorption spectroscopy, and were compared to national and state limits, as well as the Kirksville water report. |
| Cole J. Prentiss, Tucker C. Maxwell, and Lyle Raine | Activities Room | 14:30 | Effectiveness of Water Purification Methods on Metal Content as Determined by GFAAS | Water quality does not change in a linear fashion: The presence of both biological and chemical contaminants can fluctuate wildly. While governments across the United States are working to replace old plumbing infrastructure like lead piping, the problem of heavy metal poisoning persists in many regions of the country. The most common method for a person to clean their drinking water is to bring it to a boil for at least 1 minute; however, this is more targeted towards biological contaminants like pathogens or other parasites. This experiment seeks to test the effects of various methods of water filtration and purification on specifically the heavy metal content of water using Graphite Furnace Atomic Absorption Spectrometry analysis in order to determine the most efficient methods of removing heavy metals from drinking water. |